1932

Abstract

Chronic inflammation increases the risk of several cancers, including gastric, colon, and hepatic cancers. Conversely, tumors, similar to tissue injury, trigger an inflammatory response coordinated by the innate immune system. Cellular and molecular mediators of inflammation modulate tumor growth directly and by influencing the adaptive immune response. Depending on the balance of immune cell types and signals within the tumor microenvironment, inflammation can support or restrain the tumor. Adding to the complexity, research from the past two decades has revealed that innate immune cells are highly heterogeneous and plastic, with variable phenotypes depending on tumor type, stage, and treatment. The field is now on the cusp of being able to harness this wealth of data to () classify tumors on the basis of their immune makeup, with implications for prognosis, treatment choice, and clinical outcome, and () design therapeutic strategies that activate antitumor immune responses by targeting innate immune cells.

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2022-01-24
2024-03-28
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Literature Cited

  1. 1. 
    Virchow R. 1989 (1858). Cellular pathology. As based upon physiological and pathological histology. Lecture XVI–Atheromatous affection of arteries. Nutr. Rev. 47:23–25
    [Google Scholar]
  2. 2. 
    Oelschlaeger TA. 2010. Bacteria as tumor therapeutics?. Bioeng. Bugs 1:146–47
    [Google Scholar]
  3. 3. 
    Coley WB. 1991 (1893). The treatment of malignant tumors by repeated inoculations of erysipelas. With a report of ten original cases. Clin. Orthop. Relat. Res. 262:3–11
    [Google Scholar]
  4. 4. 
    Starnes CO. 1992. Coley's toxins in perspective. Nature 357:11–12
    [Google Scholar]
  5. 5. 
    Balkwill F, Mantovani A. 2001. Inflammation and cancer: back to Virchow?. Lancet 357:539–45
    [Google Scholar]
  6. 6. 
    Starkey JR, Crowle PK, Taubenberger S. 1988. Mast-cell-deficient W/Wv mice exhibit a decreased rate of tumor angiogenesis. Int. J. Cancer 42:48–52
    [Google Scholar]
  7. 7. 
    Coussens LM, Raymond WW, Bergers G, Laig-Webster M, Behrendtsen O et al. 1999. Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis. Genes Dev. 13:1382–97
    [Google Scholar]
  8. 8. 
    Bergers G, Brekken R, McMahon G, Vu TH, Itoh T et al. 2000. Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat. Cell Biol. 2:737–44
    [Google Scholar]
  9. 9. 
    Coussens LM, Tinkle CL, Hanahan D, Werb Z 2000. MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell 103:481–90
    [Google Scholar]
  10. 10. 
    Lin EY, Nguyen AV, Russell RG, Pollard JW 2001. Colony-stimulating factor 1 promotes progression of mammary tumors to malignancy. J. Exp. Med. 193:727–40
    [Google Scholar]
  11. 11. 
    Lin EY, Li JF, Gnatovskiy L, Deng Y, Zhu L et al. 2006. Macrophages regulate the angiogenic switch in a mouse model of breast cancer. Cancer Res. 66:11238–46
    [Google Scholar]
  12. 12. 
    Greten FR, Eckmann L, Greten TF, Park JM, Li ZW et al. 2004. IKKβ links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell 118:285–96
    [Google Scholar]
  13. 13. 
    De Palma M, Venneri MA, Galli R, Sergi Sergi L, Politi LS et al. 2005. Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. Cancer Cell 8:211–26
    [Google Scholar]
  14. 14. 
    Netea MG, Balkwill F, Chonchol M, Cominelli F, Donath MY et al. 2017. A guiding map for inflammation. Nat. Immunol. 18:826–31
    [Google Scholar]
  15. 15. 
    Hossain M, Kubes P. 2019. Innate immune cells orchestrate the repair of sterile injury in the liver and beyond. Eur. J. Immunol. 49:831–41
    [Google Scholar]
  16. 16. 
    Wang J. 2018. Neutrophils in tissue injury and repair. Cell Tissue Res. 371:531–39
    [Google Scholar]
  17. 17. 
    Castanheira FVS, Kubes P. 2019. Neutrophils and NETs in modulating acute and chronic inflammation. Blood 133:2178–85
    [Google Scholar]
  18. 18. 
    Headland SE, Norling LV. 2015. The resolution of inflammation: principles and challenges. Semin. Immunol. 27:149–60
    [Google Scholar]
  19. 19. 
    Nathan C, Ding A. 2010. Nonresolving inflammation. Cell 140:871–82
    [Google Scholar]
  20. 20. 
    Dvorak HF. 1986. Tumors: wounds that do not heal. Similarities between tumor stroma generation and wound healing. N. Engl. J. Med. 315:1650–59
    [Google Scholar]
  21. 21. 
    Watson J, Salisbury C, Banks J, Whiting P, Hamilton W. 2019. Predictive value of inflammatory markers for cancer diagnosis in primary care: a prospective cohort study using electronic health records. Br. J. Cancer 120:1045–51
    [Google Scholar]
  22. 22. 
    Islami F, Goding Sauer A, Miller KD, Siegel RL, Fedewa SA et al. 2018. Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States. CA Cancer J. Clin. 68:31–54
    [Google Scholar]
  23. 23. 
    de Martel C, Georges D, Bray F, Ferlay J, Clifford GM 2020. Global burden of cancer attributable to infections in 2018: a worldwide incidence analysis. Lancet Glob. Health 8:e180–90
    [Google Scholar]
  24. 24. 
    Grivennikov SI, Greten FR, Karin M. 2010. Immunity, inflammation, and cancer. Cell 140:883–99
    [Google Scholar]
  25. 25. 
    Mantovani A, Allavena P, Sica A, Balkwill F. 2008. Cancer-related inflammation. Nature 454:436–44
    [Google Scholar]
  26. 26. 
    Moore PS, Chang Y. 2010. Why do viruses cause cancer? Highlights of the first century of human tumour virology. Nat. Rev. Cancer 10:878–89
    [Google Scholar]
  27. 27. 
    Kappelman MD, Farkas DK, Long MD, Erichsen R, Sandler RS et al. 2014. Risk of cancer in patients with inflammatory bowel diseases: a nationwide population-based cohort study with 30 years of follow-up evaluation. Clin. Gastroenterol. Hepatol. 12:265–73.e1
    [Google Scholar]
  28. 28. 
    Vujasinovic M, Dugic A, Maisonneuve P, Aljic A, Berggren R et al. 2020. Risk of developing pancreatic cancer in patients with chronic pancreatitis. J. Clin. Med. 9:3720
    [Google Scholar]
  29. 29. 
    Mouronte-Roibás C, Leiro-Fernández V, Fernández-Villar A, Botana-Rial M, Ramos-Hernández C, Ruano-Ravina A. 2016. COPD, emphysema and the onset of lung cancer. A systematic review. Cancer Lett. 382:240–44
    [Google Scholar]
  30. 30. 
    Iyengar NM, Hudis CA, Dannenberg AJ. 2015. Obesity and cancer: local and systemic mechanisms. Annu. Rev. Med. 66:297–309
    [Google Scholar]
  31. 31. 
    Quail DF, Olson OC, Bhardwaj P, Walsh LA, Akkari L et al. 2017. Obesity alters the lung myeloid cell landscape to enhance breast cancer metastasis through IL5 and GM-CSF. Nat. Cell Biol. 19:974–87
    [Google Scholar]
  32. 32. 
    Rothwell PM, Fowkes FG, Belch JF, Ogawa H, Warlow CP, Meade TW. 2011. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet 377:31–41
    [Google Scholar]
  33. 33. 
    McCormack VA, Hung RJ, Brenner DR, Bickeboller H, Rosenberger A et al. 2011. Aspirin and NSAID use and lung cancer risk: a pooled analysis in the International Lung Cancer Consortium (ILCCO). Cancer Causes Control 22:1709–20
    [Google Scholar]
  34. 34. 
    Ridker PM, MacFadyen JG, Thuren T, Everett BM, Libby P et al. 2017. Effect of interleukin-1β inhibition with canakinumab on incident lung cancer in patients with atherosclerosis: exploratory results from a randomised, double-blind, placebo-controlled trial. Lancet 390:1833–42
    [Google Scholar]
  35. 35. 
    Novartis 2021. Novartis provides update on phase III study evaluating canakinumab (ACZ885) as second or third-line treatment in combination with chemotherapy in non-small cell lung cancer Media Release. Mar. 9. https://www.novartis.com/news/media-releases/novartis-provides-update-phase-iii-study-evaluating-canakinumab-acz885-second-or-third-line-treatment-combination-chemotherapy-non-small-cell-lung-cancer
  36. 36. 
    Wellenstein MD, de Visser KE. 2018. Cancer-cell-intrinsic mechanisms shaping the tumor immune landscape. Immunity 48:399–416
    [Google Scholar]
  37. 37. 
    Burn J, Gerdes A-M, Macrae F, Mecklin J-P, Moeslein G et al. 2011. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet 378:2081–87
    [Google Scholar]
  38. 38. 
    Bezzi M, Seitzer N, Ishikawa T, Reschke M, Chen M et al. 2018. Diverse genetic-driven immune landscapes dictate tumor progression through distinct mechanisms. Nat. Med. 24:165–75
    [Google Scholar]
  39. 39. 
    Wellenstein MD, Coffelt SB, Duits DEM, van Miltenburg MH, Slagter M et al. 2019. Loss of p53 triggers WNT-dependent systemic inflammation to drive breast cancer metastasis. Nature 572:538–42
    [Google Scholar]
  40. 40. 
    Hernandez C, Huebener P, Schwabe RF. 2016. Damage-associated molecular patterns in cancer: a double-edged sword. Oncogene 35:5931–41
    [Google Scholar]
  41. 41. 
    Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C et al. 2007. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat. Med. 13:1050–59
    [Google Scholar]
  42. 42. 
    He SJ, Cheng J, Feng X, Yu Y, Tian L, Huang Q 2017. The dual role and therapeutic potential of high-mobility group box 1 in cancer. Oncotarget 8:64534–50
    [Google Scholar]
  43. 43. 
    Pitt JM, Kroemer G, Zitvogel L. 2017. Immunogenic and non-immunogenic cell death in the tumor microenvironment. Adv. Exp. Med. Biol. 1036:65–79
    [Google Scholar]
  44. 44. 
    Hegde S, Krisnawan VE, Herzog BH, Zuo C, Breden MA et al. 2020. Dendritic cell paucity leads to dysfunctional immune surveillance in pancreatic cancer. Cancer Cell 37:289–307.e9
    [Google Scholar]
  45. 45. 
    Wynn TA, Chawla A, Pollard JW. 2013. Macrophage biology in development, homeostasis and disease. Nature 496:445–55
    [Google Scholar]
  46. 46. 
    Gentles AJ, Newman AM, Liu CL, Bratman SV, Feng W et al. 2015. The prognostic landscape of genes and infiltrating immune cells across human cancers. Nat. Med. 21:938–45
    [Google Scholar]
  47. 47. 
    Noy R, Pollard JW. 2014. Tumor-associated macrophages: from mechanisms to therapy. Immunity 41:49–61
    [Google Scholar]
  48. 48. 
    Sun L, Kees T, Santos Almeida A, Liu B, He X-Y et al. 2021. Activating a collaborative innate-adaptive immune response to control metastasis. Cancer Cell 39:101361–74.e9
    [Google Scholar]
  49. 49. 
    DeNardo DG, Barreto JB, Andreu P, Vasquez L, Tawfik D et al. 2009. CD4+ T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell 16:91–102
    [Google Scholar]
  50. 50. 
    Colegio OR, Chu N-Q, Szabo AL, Chu T, Rhebergen AM et al. 2014. Functional polarization of tumour-associated macrophages by tumour-derived lactic acid. Nature 513:559–63
    [Google Scholar]
  51. 51. 
    Andreu P, Johansson M, Affara NI, Pucci F, Tan T et al. 2010. FcRγ activation regulates inflammation-associated squamous carcinogenesis. Cancer Cell 17:121–34
    [Google Scholar]
  52. 52. 
    Imtiyaz HZ, Williams EP, Hickey MM, Patel SA, Durham AC et al. 2010. Hypoxia-inducible factor 2α regulates macrophage function in mouse models of acute and tumor inflammation. J. Clin. Investig. 120:2699–714
    [Google Scholar]
  53. 53. 
    Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW et al. 2014. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity 41:14–20
    [Google Scholar]
  54. 54. 
    Gubin MM, Esaulova E, Ward JP, Malkova ON, Runci D et al. 2018. High-dimensional analysis delineates myeloid and lymphoid compartment remodeling during successful immune-checkpoint cancer therapy. Cell 175:1014–30.e19
    [Google Scholar]
  55. 55. 
    Wyckoff JB, Wang Y, Lin EY, Li JF, Goswami S et al. 2007. Direct visualization of macrophage-assisted tumor cell intravasation in mammary tumors. Cancer Res. 67:2649–56
    [Google Scholar]
  56. 56. 
    Su S, Liu Q, Chen J, Chen J, Chen F et al. 2014. A positive feedback loop between mesenchymal-like cancer cells and macrophages is essential to breast cancer metastasis. Cancer Cell 25:605–20
    [Google Scholar]
  57. 57. 
    Chen Q, Zhang XH, Massague J. 2011. Macrophage binding to receptor VCAM-1 transmits survival signals in breast cancer cells that invade the lungs. Cancer Cell 20:538–49
    [Google Scholar]
  58. 58. 
    Ruffell B, Chang-Strachan D, Chan V, Rosenbusch A, Ho CM et al. 2014. Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells. Cancer Cell 26:623–37
    [Google Scholar]
  59. 59. 
    Mantovani A, Allavena P. 2015. The interaction of anticancer therapies with tumor-associated macrophages. J. Exp. Med. 212:435–45
    [Google Scholar]
  60. 60. 
    Arlauckas SP, Garris CS, Kohler RH, Kitaoka M, Cuccarese MF et al. 2017. In vivo imaging reveals a tumor-associated macrophage-mediated resistance pathway in anti-PD-1 therapy. Sci. Transl. Med. 9:eaal3604
    [Google Scholar]
  61. 61. 
    Gordon SR, Maute RL, Dulken BW, Hutter G, George BM et al. 2017. PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity. Nature 545:495–99
    [Google Scholar]
  62. 62. 
    Pyonteck SM, Akkari L, Schuhmacher AJ, Bowman RL, Sevenich L et al. 2013. CSF-1R inhibition alters macrophage polarization and blocks glioma progression. Nat. Med. 19:1264–72
    [Google Scholar]
  63. 63. 
    Liew PX, Kubes P. 2019. The neutrophil's role during health and disease. Physiol. Rev. 99:1223–48
    [Google Scholar]
  64. 64. 
    Keizman D, Ish-Shalom M, Huang P, Eisenberger MA, Pili R et al. 2012. The association of pre-treatment neutrophil to lymphocyte ratio with response rate, progression free survival and overall survival of patients treated with sunitinib for metastatic renal cell carcinoma. Eur. J. Cancer 48:202–8
    [Google Scholar]
  65. 65. 
    Donskov F. 2013. Immunomonitoring and prognostic relevance of neutrophils in clinical trials. Semin. Cancer Biol. 23:200–7
    [Google Scholar]
  66. 66. 
    Jablonska J, Leschner S, Westphal K, Lienenklaus S, Weiss S 2010. Neutrophils responsive to endogenous IFN-β regulate tumor angiogenesis and growth in a mouse tumor model. J. Clin. Investig. 120:1151–64
    [Google Scholar]
  67. 67. 
    Coffelt SB, Wellenstein MD, de Visser KE. 2016. Neutrophils in cancer: neutral no more. Nat. Rev. Cancer 16:431–46
    [Google Scholar]
  68. 68. 
    Fridlender ZG, Sun J, Kim S, Kapoor V, Cheng G et al. 2009. Polarization of tumor-associated neutrophil phenotype by TGF-β: “N1” versus “N2” TAN. Cancer Cell 16:183–94
    [Google Scholar]
  69. 69. 
    Jablonska J, Leschner S, Westphal K, Lienenklaus S, Weiss S 2010. Neutrophils responsive to endogenous IFN-β regulate tumor angiogenesis and growth in a mouse tumor model. J. Clin. Investig. 120:1151–64
    [Google Scholar]
  70. 70. 
    Welch DR, Schissel DJ, Howrey RP, Aeed PA. 1989. Tumor-elicited polymorphonuclear cells, in contrast to “normal” circulating polymorphonuclear cells, stimulate invasive and metastatic potentials of rat mammary adenocarcinoma cells. PNAS 86:5859–63
    [Google Scholar]
  71. 71. 
    Bald T, Quast T, Landsberg J, Rogava M, Glodde N et al. 2014. Ultraviolet-radiation-induced inflammation promotes angiotropism and metastasis in melanoma. Nature 507:109–13
    [Google Scholar]
  72. 72. 
    Spicer JD, McDonald B, Cools-Lartigue JJ, Chow SC, Giannias B et al. 2012. Neutrophils promote liver metastasis via Mac-1-mediated interactions with circulating tumor cells. Cancer Res. 72:3919–27
    [Google Scholar]
  73. 73. 
    Yan HH, Pickup M, Pang Y, Gorska AE, Li Z et al. 2010. Gr-1+CD11b+ myeloid cells tip the balance of immune protection to tumor promotion in the premetastatic lung. Cancer Res. 70:6139–49
    [Google Scholar]
  74. 74. 
    Kowanetz M, Wu X, Lee J, Tan M, Hagenbeek T et al. 2010. Granulocyte-colony stimulating factor promotes lung metastasis through mobilization of Ly6G+Ly6C+ granulocytes. PNAS 107:21248–55
    [Google Scholar]
  75. 75. 
    Patel S, Fu S, Mastio J, Dominguez GA, Purohit A et al. 2018. Unique pattern of neutrophil migration and function during tumor progression. Nat. Immunol. 19:1236–47
    [Google Scholar]
  76. 76. 
    Wculek SK, Malanchi I. 2015. Neutrophils support lung colonization of metastasis-initiating breast cancer cells. Nature 528:413–17
    [Google Scholar]
  77. 77. 
    Coffelt SB, Kersten K, Doornebal CW, Weiden J, Vrijland K et al. 2015. IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis. Nature 522:345–48
    [Google Scholar]
  78. 78. 
    Catena R, Bhattacharya N, El Rayes T, Wang S, Choi H et al. 2013. Bone marrow–derived Gr1+ cells can generate a metastasis-resistant microenvironment via induced secretion of thrombospondin-1. Cancer Discov. 3:578–89
    [Google Scholar]
  79. 79. 
    Finisguerra V, Di Conza G, Di Matteo M, Serneels J, Costa S et al. 2015. MET is required for the recruitment of anti-tumoural neutrophils. Nature 522:349–53
    [Google Scholar]
  80. 80. 
    Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y et al. 2004. Neutrophil extracellular traps kill bacteria. Science 303:1532–35
    [Google Scholar]
  81. 81. 
    Cools-Lartigue J, Spicer J, McDonald B, Gowing S, Chow S et al. 2013. Neutrophil extracellular traps sequester circulating tumor cells and promote metastasis. J. Clin. Investig. 123:3446–58
    [Google Scholar]
  82. 82. 
    Tohme S, Yazdani HO, Al-Khafaji AB, Chidi AP, Loughran P et al. 2016. Neutrophil extracellular traps promote the development and progression of liver metastases after surgical stress. Cancer Res 76:1367–80
    [Google Scholar]
  83. 83. 
    Lee W, Ko SY, Mohamed MS, Kenny HA, Lengyel E, Naora H 2019. Neutrophils facilitate ovarian cancer premetastatic niche formation in the omentum. J. Exp. Med. 216:176–94
    [Google Scholar]
  84. 84. 
    Park J, Wysocki RW, Amoozgar Z, Maiorino L, Fein MR et al. 2016. Cancer cells induce metastasis-supporting neutrophil extracellular DNA traps. Sci. Transl. Med. 8:361ra138
    [Google Scholar]
  85. 85. 
    Yang L, Liu Q, Zhang X, Liu X, Zhou B et al. 2020. DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25. Nature 583:133–38
    [Google Scholar]
  86. 86. 
    Albrengues J, Shields MA, Ng D, Park CG, Ambrico A et al. 2018. Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice. Science 361:eaao4227
    [Google Scholar]
  87. 87. 
    Teijeira A, Garasa S, Gato M, Alfaro C, Migueliz I et al. 2020. CXCR1 and CXCR2 chemokine receptor agonists produced by tumors induce neutrophil extracellular traps that interfere with immune cytotoxicity. Immunity 52:856–71.e8
    [Google Scholar]
  88. 88. 
    Veglia F, Perego M, Gabrilovich D. 2018. Myeloid-derived suppressor cells coming of age. Nat. Immunol. 19:108–19
    [Google Scholar]
  89. 89. 
    Geiger R, Rieckmann JC, Wolf T, Basso C, Feng Y et al. 2016. l-arginine modulates T cell metabolism and enhances survival and anti-tumor activity. Cell 167:829–42.e13
    [Google Scholar]
  90. 90. 
    Harari O, Liao JK. 2004. Inhibition of MHC II gene transcription by nitric oxide and antioxidants. Curr. Pharm. Des. 10:893–98
    [Google Scholar]
  91. 91. 
    Baumann T, Dunkel A, Schmid C, Schmitt S, Hiltensperger M et al. 2020. Regulatory myeloid cells paralyze T cells through cell-cell transfer of the metabolite methylglyoxal. Nat. Immunol. 21:555–66
    [Google Scholar]
  92. 92. 
    Lu Z, Zou J, Li S, Topper MJ, Tao Y et al. 2020. Epigenetic therapy inhibits metastases by disrupting premetastatic niches. Nature 579:284–90
    [Google Scholar]
  93. 93. 
    Meyer C, Cagnon L, Costa-Nunes CM, Baumgaertner P, Montandon N et al. 2014. Frequencies of circulating MDSC correlate with clinical outcome of melanoma patients treated with ipilimumab. Cancer Immunol. Immunother. 63:247–57
    [Google Scholar]
  94. 94. 
    Highfill SL, Cui Y, Giles AJ, Smith JP, Zhang H et al. 2014. Disruption of CXCR2-mediated MDSC tumor trafficking enhances anti-PD1 efficacy. Sci. Transl. Med. 6:237ra67
    [Google Scholar]
  95. 95. 
    Steinman RM. 1991. The dendritic cell system and its role in immunogenicity. Annu. Rev. Immunol. 9:271–96
    [Google Scholar]
  96. 96. 
    Villadangos JA, Schnorrer P. 2007. Intrinsic and cooperative antigen-presenting functions of dendritic-cell subsets in vivo. Nat. Rev. Immunol. 7:543–55
    [Google Scholar]
  97. 97. 
    Hildner K, Edelson BT, Purtha WE, Diamond M, Matsushita H et al. 2008. Batf3 deficiency reveals a critical role for CD8α+ dendritic cells in cytotoxic T cell immunity. Science 322:1097–100
    [Google Scholar]
  98. 98. 
    Broz ML, Binnewies M, Boldajipour B, Nelson AE, Pollack JL et al. 2014. Dissecting the tumor myeloid compartment reveals rare activating antigen-presenting cells critical for T cell immunity. Cancer Cell 26:638–52
    [Google Scholar]
  99. 99. 
    Lai J, Mardiana S, House IG, Sek K, Henderson MA et al. 2020. Adoptive cellular therapy with T cells expressing the dendritic cell growth factor Flt3L drives epitope spreading and antitumor immunity. Nat. Immunol. 21:914–26
    [Google Scholar]
  100. 100. 
    Spranger S, Dai D, Horton B, Gajewski TF. 2017. Tumor-residing Batf3 dendritic cells are required for effector T cell trafficking and adoptive T cell therapy. Cancer Cell 31:711–23.e4
    [Google Scholar]
  101. 101. 
    Salmon H, Idoyaga J, Rahman A, Leboeuf M, Remark R et al. 2016. Expansion and activation of CD103+ dendritic cell progenitors at the tumor site enhances tumor responses to therapeutic PD-L1 and BRAF inhibition. Immunity 44:924–38
    [Google Scholar]
  102. 102. 
    Yang H, Xia L, Chen J, Zhang S, Martin V et al. 2019. Stress-glucocorticoid-TSC22D3 axis compromises therapy-induced antitumor immunity. Nat. Med. 25:1428–41
    [Google Scholar]
  103. 103. 
    Swiecki M, Colonna M. 2015. The multifaceted biology of plasmacytoid dendritic cells. Nat. Rev. Immunol. 15:471–85
    [Google Scholar]
  104. 104. 
    Treilleux I, Blay J-Y, Bendriss-Vermare N, Ray-Coquard I, Bachelot T et al. 2004. Dendritic cell infiltration and prognosis of early stage breast cancer. Clin. Cancer Res. 10:7466–74
    [Google Scholar]
  105. 105. 
    Labidi-Galy SI, Treilleux I, Goddard-Leon S, Combes JD, Blay J-Y et al. 2012. Plasmacytoid dendritic cells infiltrating ovarian cancer are associated with poor prognosis. Oncoimmunology 1:380–82
    [Google Scholar]
  106. 106. 
    Poropatich K, Dominguez D, Chan W-C, Andrade J, Zha Y et al. 2020. OX40+ plasmacytoid dendritic cells in the tumor microenvironment promote antitumor immunity. J. Clin. Investig. 130:3528–42
    [Google Scholar]
  107. 107. 
    Sisirak V, Faget J, Gobert M, Goutagny N, Vey N et al. 2012. Impaired IFN-α production by plasmacytoid dendritic cells favors regulatory T-cell expansion that may contribute to breast cancer progression. Cancer Res. 72:5188–97
    [Google Scholar]
  108. 108. 
    Terra M, Oberkampf M, Fayolle C, Rosenbaum P, Guillerey C et al. 2018. Tumor-derived TGFβ alters the ability of plasmacytoid dendritic cells to respond to innate immune signaling. Cancer Res. 78:3014–26
    [Google Scholar]
  109. 109. 
    Chen W, Liang X, Peterson AJ, Munn DH, Blazar BR. 2008. The indoleamine 2,3-dioxygenase pathway is essential for human plasmacytoid dendritic cell-induced adaptive T regulatory cell generation. J. Immunol. 181:5396–404
    [Google Scholar]
  110. 110. 
    Conrad C, Gregorio J, Wang YH, Ito T, Meller S et al. 2012. Plasmacytoid dendritic cells promote immunosuppression in ovarian cancer via ICOS costimulation of Foxp3+ T-regulatory cells. Cancer Res. 72:5240–49
    [Google Scholar]
  111. 111. 
    Binnewies M, Mujal AM, Pollack JL, Combes AJ, Hardison EA et al. 2019. Unleashing type-2 dendritic cells to drive protective antitumor CD4+ T cell immunity. Cell 177:556–71.e16
    [Google Scholar]
  112. 112. 
    Maier B, Leader AM, Chen ST, Tung N, Chang C et al. 2020. A conserved dendritic-cell regulatory program limits antitumour immunity. Nature 580:257–62
    [Google Scholar]
  113. 113. 
    Lu T, Ramakrishnan R, Altiok S, Youn J-I, Cheng P et al. 2011. Tumor-infiltrating myeloid cells induce tumor cell resistance to cytotoxic T cells in mice. J. Clin. Investig. 121:4015–29
    [Google Scholar]
  114. 114. 
    Vivier E, Artis D, Colonna M, Diefenbach A, Di Santo JP et al. 2018. Innate lymphoid cells: 10 years on. Cell 174:1054–66
    [Google Scholar]
  115. 115. 
    Jovanovic IP, Pejnovic NN, Radosavljevic GD, Pantic JM, Milovanovic MZ et al. 2014. Interleukin-33/ST2 axis promotes breast cancer growth and metastases by facilitating intratumoral accumulation of immunosuppressive and innate lymphoid cells. Int. J. Cancer 134:1669–82
    [Google Scholar]
  116. 116. 
    Moral JA, Leung J, Rojas LA, Ruan J, Zhao J et al. 2020. ILC2s amplify PD-1 blockade by activating tissue-specific cancer immunity. Nature 579:130–35
    [Google Scholar]
  117. 117. 
    Ikutani M, Yanagibashi T, Ogasawara M, Tsuneyama K, Yamamoto S et al. 2012. Identification of innate IL-5-producing cells and their role in lung eosinophil regulation and antitumor immunity. J. Immunol. 188:703–13
    [Google Scholar]
  118. 118. 
    Dadi S, Chhangawala S, Whitlock BM, Franklin RA, Luo CT et al. 2016. Cancer immunosurveillance by tissue-resident innate lymphoid cells and innate-like T cells. Cell 164:365–77
    [Google Scholar]
  119. 119. 
    Gao Y, Souza-Fonseca-Guimaraes F, Bald T, Ng SS, Young A et al. 2017. Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells. Nat. Immunol. 18:1004–15
    [Google Scholar]
  120. 120. 
    Cortez VS, Ulland TK, Cervantes-Barragan L, Bando JK, Robinette ML et al. 2017. SMAD4 impedes the conversion of NK cells into ILC1-like cells by curtailing non-canonical TGF-β signaling. Nat. Immunol. 18:995–1003
    [Google Scholar]
  121. 121. 
    Shields JD, Kourtis IC, Tomei AA, Roberts JM, Swartz MA. 2010. Induction of lymphoidlike stroma and immune escape by tumors that express the chemokine CCL21. Science 328:749–52
    [Google Scholar]
  122. 122. 
    Carrega P, Loiacono F, Di Carlo E, Scaramuccia A, Mora M et al. 2015. NCR+ILC3 concentrate in human lung cancer and associate with intratumoral lymphoid structures. Nat. Commun. 6:8280
    [Google Scholar]
  123. 123. 
    Talmadge JE, Meyers KM, Prieur DJ, Starkey JR. 1980. Role of NK cells in tumour growth and metastasis in beige mice. Nature 284:622–24
    [Google Scholar]
  124. 124. 
    Coca S, Perez-Piqueras J, Martinez D, Colmenarejo A, Saez MA et al. 1997. The prognostic significance of intratumoral natural killer cells in patients with colorectal carcinoma. Cancer 79:2320–28
    [Google Scholar]
  125. 125. 
    Mastaglio S, Wong E, Perera T, Ripley J, Blombery P et al. 2018. Natural killer receptor ligand expression on acute myeloid leukemia impacts survival and relapse after chemotherapy. Blood Adv 2:335–46
    [Google Scholar]
  126. 126. 
    Stringaris K, Sekine T, Khoder A, Alsuliman A, Razzaghi B et al. 2014. Leukemia-induced phenotypic and functional defects in natural killer cells predict failure to achieve remission in acute myeloid leukemia. Haematologica 99:836–47
    [Google Scholar]
  127. 127. 
    van den Broek MF, Kägi D, Zinkernagel RM, Hengartner H. 1995. Perforin dependence of natural killer cell-mediated tumor control in vivo. Eur. J. Immunol. 25:3514–16
    [Google Scholar]
  128. 128. 
    Kärre K, Ljunggren HG, Piontek G, Kiessling R 1986. Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature 319:675–78
    [Google Scholar]
  129. 129. 
    Diefenbach A, Jensen ER, Jamieson AM, Raulet DH. 2001. Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity. Nature 413:165–71
    [Google Scholar]
  130. 130. 
    Gasser S, Orsulic S, Brown EJ, Raulet DH. 2005. The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature 436:1186–90
    [Google Scholar]
  131. 131. 
    Guerra N, Tan YX, Joncker NT, Choy A, Gallardo F et al. 2008. NKG2D-deficient mice are defective in tumor surveillance in models of spontaneous malignancy. Immunity 28:571–80
    [Google Scholar]
  132. 132. 
    Glasner A, Ghadially H, Gur C, Stanietsky N, Tsukerman P et al. 2012. Recognition and prevention of tumor metastasis by the NK receptor NKp46/NCR1. J. Immunol. 188:2509–15
    [Google Scholar]
  133. 133. 
    Costello RT, Sivori S, Marcenaro E, Lafage-Pochitaloff M, Mozziconacci MJ et al. 2002. Defective expression and function of natural killer cell-triggering receptors in patients with acute myeloid leukemia. Blood 99:3661–67
    [Google Scholar]
  134. 134. 
    Barry KC, Hsu J, Broz ML, Cueto FJ, Binnewies M et al. 2018. A natural killer–dendritic cell axis defines checkpoint therapy–responsive tumor microenvironments. Nat. Med. 24:1178–91
    [Google Scholar]
  135. 135. 
    Bottcher JP, Bonavita E, Chakravarty P, Blees H, Cabeza-Cabrerizo M et al. 2018. NK cells stimulate recruitment of cDC1 into the tumor microenvironment promoting cancer immune control. Cell 172:1022–37.e14
    [Google Scholar]
  136. 136. 
    Mittal D, Vijayan D, Putz EM, Aguilera AR, Markey KA et al. 2017. Interleukin-12 from CD103+ Batf3-dependent dendritic cells required for NK-cell suppression of metastasis. Cancer Immunol. Res. 5:1098–108
    [Google Scholar]
  137. 137. 
    Delconte RB, Kolesnik TB, Dagley LF, Rautela J, Shi W et al. 2016. CIS is a potent checkpoint in NK cell–mediated tumor immunity. Nat. Immunol. 17:816–24
    [Google Scholar]
  138. 138. 
    Ohs I, Ducimetière L, Marinho J, Kulig P, Becher B, Tugues S. 2017. Restoration of natural killer cell antimetastatic activity by IL12 and checkpoint blockade. Cancer Res. 77:7059–71
    [Google Scholar]
  139. 139. 
    Zhang Q, Bi J, Zheng X, Chen Y, Wang H et al. 2018. Blockade of the checkpoint receptor TIGIT prevents NK cell exhaustion and elicits potent anti-tumor immunity. Nat. Immunol. 19:723–32
    [Google Scholar]
  140. 140. 
    Molgora M, Bonavita E, Ponzetta A, Riva F, Barbagallo M et al. 2017. IL-1R8 is a checkpoint in NK cells regulating anti-tumour and anti-viral activity. Nature 551:110–14
    [Google Scholar]
  141. 141. 
    Niu C, Jin H, Li M, Xu J, Xu D et al. 2015. In vitro analysis of the proliferative capacity and cytotoxic effects of ex vivo induced natural killer cells, cytokine-induced killer cells, and gamma-delta T cells. BMC Immunol. 16:61
    [Google Scholar]
  142. 142. 
    Dokouhaki P, Schuh NW, Joe B, Allen CA, Der SD et al. 2013. NKG2D regulates production of soluble TRAIL by ex vivo expanded human γδ T cells. Eur. J. Immunol. 43:3175–82
    [Google Scholar]
  143. 143. 
    Gao Y, Yang W, Pan M, Scully E, Girardi M et al. 2003. γδ T cells provide an early source of interferon γ in tumor immunity. J. Exp. Med. 198:433–42
    [Google Scholar]
  144. 144. 
    Maniar A, Zhang X, Lin W, Gastman BR, Pauza CD et al. 2010. Human γδ T lymphocytes induce robust NK cell–mediated antitumor cytotoxicity through CD137 engagement. Blood 116:1726–33
    [Google Scholar]
  145. 145. 
    Jin C, Lagoudas GK, Zhao C, Bullman S, Bhutkar A et al. 2019. Commensal microbiota promote lung cancer development via γδ T cells. Cell 176:998–1013.e16
    [Google Scholar]
  146. 146. 
    Daley D, Zambirinis CP, Seifert L, Akkad N, Mohan N et al. 2016. γδ T cells support pancreatic oncogenesis by restraining αβ T cell activation. Cell 166:1485–99.e15
    [Google Scholar]
  147. 147. 
    Cui J, Shin T, Kawano T, Sato H, Kondo E et al. 1997. Requirement for Vα14 NKT cells in IL-12-mediated rejection of tumors. Science 278:1623–26
    [Google Scholar]
  148. 148. 
    De Santo C, Arscott R, Booth S, Karydis I, Jones M et al. 2010. Invariant NKT cells modulate the suppressive activity of IL-10-secreting neutrophils differentiated with serum amyloid A. Nat. Immunol. 11:1039–46
    [Google Scholar]
  149. 149. 
    Hermans IF, Silk JD, Gileadi U, Salio M, Mathew B et al. 2003. NKT cells enhance CD4+ and CD8+ T cell responses to soluble antigen in vivo through direct interaction with dendritic cells. J. Immunol. 171:5140–47
    [Google Scholar]
  150. 150. 
    Semmling V, Lukacs-Kornek V, Thaiss CA, Quast T, Hochheiser K et al. 2010. Alternative cross-priming through CCL17-CCR4-mediated attraction of CTLs toward NKT cell–licensed DCs. Nat. Immunol. 11:313–20
    [Google Scholar]
  151. 151. 
    Bae E-A, Seo H, Kim B-S, Choi J, Jeon I et al. 2018. Activation of NKT cells in an anti-PD-1-resistant tumor model enhances antitumor immunity by reinvigorating exhausted CD8 T cells. Cancer Res. 78:5315–26
    [Google Scholar]
  152. 152. 
    Terabe M, Swann J, Ambrosino E, Sinha P, Takaku S et al. 2005. A nonclassical non-Vα14Jα18 CD1d-restricted (type II) NKT cell is sufficient for down-regulation of tumor immunosurveillance. J. Exp. Med. 202:1627–33
    [Google Scholar]
  153. 153. 
    Ambrosino E, Terabe M, Halder RC, Peng J, Takaku S et al. 2007. Cross-regulation between type I and type II NKT cells in regulating tumor immunity: a new immunoregulatory axis. J. Immunol. 179:5126–36
    [Google Scholar]
  154. 154. 
    Merle NS, Church SE, Fremeaux-Bacchi V, Roumenina LT. 2015. Complement system part I – molecular mechanisms of activation and regulation. Front. Immunol. 6:262
    [Google Scholar]
  155. 155. 
    Merle NS, Noe R, Halbwachs-Mecarelli L, Fremeaux-Bacchi V, Roumenina LT. 2015. Complement system part II: role in immunity. Front. Immunol. 6:257
    [Google Scholar]
  156. 156. 
    Kennedy AD, Beum PV, Solga MD, DiLillo DJ, Lindorfer MA et al. 2004. Rituximab infusion promotes rapid complement depletion and acute CD20 loss in chronic lymphocytic leukemia. J. Immunol. 172:3280–88
    [Google Scholar]
  157. 157. 
    Lu Y, Zhao Q, Liao JY, Song E, Xia Q et al. 2020. Complement signals determine opposite effects of B cells in chemotherapy-induced immunity. Cell 180:1081–97.e24
    [Google Scholar]
  158. 158. 
    Corrales L, Ajona D, Rafail S, Lasarte JJ, Riezu-Boj JI et al. 2012. Anaphylatoxin C5a creates a favorable microenvironment for lung cancer progression. J. Immunol. 189:4674–83
    [Google Scholar]
  159. 159. 
    An LL, Gorman JV, Stephens G, Swerdlow B, Warrener P et al. 2016. Complement C5a induces PD-L1 expression and acts in synergy with LPS through Erk1/2 and JNK signaling pathways. Sci. Rep. 6:33346
    [Google Scholar]
  160. 160. 
    Janelle V, Langlois M-P, Tarrab E, Lapierre P, Poliquin L, Lamarre A 2014. Transient complement inhibition promotes a tumor-specific immune response through the implication of natural killer cells. Cancer Immunol. Res. 2:200–6
    [Google Scholar]
  161. 161. 
    Medler TR, Murugan D, Horton W, Kumar S, Cotechini T et al. 2018. Complement C5a fosters squamous carcinogenesis and limits T cell response to chemotherapy. Cancer Cell 34:561–78.e6
    [Google Scholar]
  162. 162. 
    Guglietta S, Chiavelli A, Zagato E, Krieg C, Gandini S et al. 2016. Coagulation induced by C3aR-dependent NETosis drives protumorigenic neutrophils during small intestinal tumorigenesis. Nat. Commun. 7:11037
    [Google Scholar]
  163. 163. 
    Sohn J-H, Bora PS, Suk H-J, Molina H, Kaplan HJ, Bora NS. 2003. Tolerance is dependent on complement C3 fragment iC3b binding to antigen-presenting cells. Nat. Med. 9:206–12
    [Google Scholar]
  164. 164. 
    Hsieh C-C, Chou H-S, Yang H-R, Lin F, Bhatt S et al. 2013. The role of complement component 3 (C3) in differentiation of myeloid-derived suppressor cells. Blood 121:1760–68
    [Google Scholar]
  165. 165. 
    Bonavita E, Gentile S, Rubino M, Maina V, Papait R et al. 2015. PTX3 is an extrinsic oncosuppressor regulating complement-dependent inflammation in cancer. Cell 160:700–14
    [Google Scholar]
  166. 166. 
    Pickup MW, Mouw JK, Weaver VM. 2014. The extracellular matrix modulates the hallmarks of cancer. EMBO Rep. 15:1243–53
    [Google Scholar]
  167. 167. 
    Reginato MJ, Mills KR, Paulus JK, Lynch DK, Sgroi DC et al. 2003. Integrins and EGFR coordinately regulate the pro-apoptotic protein Bim to prevent anoikis. Nat. Cell Biol. 5:733–40
    [Google Scholar]
  168. 168. 
    Mammoto A, Connor KM, Mammoto T, Yung CW, Huh D et al. 2009. A mechanosensitive transcriptional mechanism that controls angiogenesis. Nature 457:1103–8
    [Google Scholar]
  169. 169. 
    Leight JL, Wozniak MA, Chen S, Lynch ML, Chen CS 2012. Matrix rigidity regulates a switch between TGF-β1–induced apoptosis and epithelial–mesenchymal transition. Mol. Biol. Cell 23:781–91
    [Google Scholar]
  170. 170. 
    Sorokin L. 2010. The impact of the extracellular matrix on inflammation. Nat. Rev. Immunol. 10:712–23
    [Google Scholar]
  171. 171. 
    Acerbi I, Cassereau L, Dean I, Shi Q, Au A et al. 2015. Human breast cancer invasion and aggression correlates with ECM stiffening and immune cell infiltration. Integr. Biol. 7:1120–34
    [Google Scholar]
  172. 172. 
    Larsen AMH, Kuczek DE, Kalvisa A, Siersbæk MS, Thorseth M-L et al. 2020. Collagen density modulates the immunosuppressive functions of macrophages. J. Immunol. 205:1461–72
    [Google Scholar]
  173. 173. 
    Kim S, Takahashi H, Lin W-W, Descargues P, Grivennikov S et al. 2009. Carcinoma-produced factors activate myeloid cells through TLR2 to stimulate metastasis. Nature 457:102–6
    [Google Scholar]
  174. 174. 
    Rygiel TP, Stolte EH, de Ruiter T, van de Weijer ML, Meyaard L. 2011. Tumor-expressed collagens can modulate immune cell function through the inhibitory collagen receptor LAIR-1. Mol. Immunol. 49:402–6
    [Google Scholar]
  175. 175. 
    Hope C, Emmerich PB, Papadas A, Pagenkopf A, Matkowskyj KA et al. 2017. Versican-derived matrikines regulate Batf3-dendritic cell differentiation and promote T cell infiltration in colorectal cancer. J. Immunol. 199:1933–41
    [Google Scholar]
  176. 176. 
    Kalluri R. 2016. The biology and function of fibroblasts in cancer. Nat. Rev. Cancer 16:582–98
    [Google Scholar]
  177. 177. 
    Cho H, Seo Y, Loke KM, Kim S-W, Oh S-M et al. 2018. Cancer-stimulated CAFs enhance monocyte differentiation and protumoral TAM activation via IL6 and GM-CSF secretion. Clin. Cancer Res. 24:5407–21
    [Google Scholar]
  178. 178. 
    Zhang R, Qi F, Zhao F, Li G, Shao S et al. 2019. Cancer-associated fibroblasts enhance tumor-associated macrophages enrichment and suppress NK cells function in colorectal cancer. Cell Death Dis. 10:273
    [Google Scholar]
  179. 179. 
    Kumar V, Donthireddy L, Marvel D, Condamine T, Wang F et al. 2017. Cancer-associated fibroblasts neutralize the anti-tumor effect of CSF1 receptor blockade by inducing PMN-MDSC infiltration of tumors. Cancer Cell 32:654–68.e5
    [Google Scholar]
  180. 180. 
    Balsamo M, Scordamaglia F, Pietra G, Manzini C et al. 2009. Melanoma-associated fibroblasts modulate NK cell phenotype and antitumor cytotoxicity. PNAS 106:20847–52
    [Google Scholar]
  181. 181. 
    Cheng J-T, Deng Y-N, Yi H-M, Wang G-Y, Fu B-S et al. 2016. Hepatic carcinoma-associated fibroblasts induce IDO-producing regulatory dendritic cells through IL-6-mediated STAT3 activation. Oncogenesis 5:e198
    [Google Scholar]
  182. 182. 
    Cheng Y, Li H, Deng Y, Tai Y, Zeng K et al. 2018. Cancer-associated fibroblasts induce PDL1+ neutrophils through the IL6-STAT3 pathway that foster immune suppression in hepatocellular carcinoma. Cell Death Dis. 9:422
    [Google Scholar]
  183. 183. 
    Kato T, Noma K, Ohara T, Kashima H, Katsura Y et al. 2018. Cancer-associated fibroblasts affect intratumoral CD8+ and FoxP3+ T cells via IL6 in the tumor microenvironment. Clin. Cancer Res. 24:4820–33
    [Google Scholar]
  184. 184. 
    Elyada E, Bolisetty M, Laise P, Flynn WF, Courtois ET et al. 2019. Cross-species single-cell analysis of pancreatic ductal adenocarcinoma reveals antigen-presenting cancer-associated fibroblasts. Cancer Discov. 9:1102–23
    [Google Scholar]
  185. 185. 
    Feig C, Jones JO, Kraman M, Wells RJB, Deonarine A et al. 2013. Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti–PD-L1 immunotherapy in pancreatic cancer. PNAS 110:20212–17
    [Google Scholar]
  186. 186. 
    Wang Z, Yan R, Li J, Gao Y, Moresco P et al. 2020. Pancreatic cancer cells assemble a CXCL12-keratin 19 coating to resist immunotherapy. bioRxiv 776419. https://doi.org/10.1101/776419
    [Crossref]
  187. 187. 
    Biasci D, Smoragiewicz M, Connell CM, Wang Z, Gao Y et al. 2020. CXCR4 inhibition in human pancreatic and colorectal cancers induces an integrated immune response. PNAS 117:28960–70
    [Google Scholar]
  188. 188. 
    Honda K, Littman DR. 2016. The microbiota in adaptive immune homeostasis and disease. Nature 535:75–84
    [Google Scholar]
  189. 189. 
    Petrelli F, Ghidini M, Ghidini A, Perego G, Cabiddu M et al. 2019. Use of antibiotics and risk of cancer: a systematic review and meta-analysis of observational studies. Cancers 11:1174
    [Google Scholar]
  190. 190. 
    Schulz MD, Atay C, Heringer J, Romrig FK, Schwitalla S et al. 2014. High-fat-diet-mediated dysbiosis promotes intestinal carcinogenesis independently of obesity. Nature 514:508–12
    [Google Scholar]
  191. 191. 
    Grivennikov SI, Wang K, Mucida D, Stewart CA, Schnabl B et al. 2012. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature 491:254–58
    [Google Scholar]
  192. 192. 
    Ma C, Han M, Heinrich B, Fu Q, Zhang Q et al. 2018. Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells. Science 360:eaan5931
    [Google Scholar]
  193. 193. 
    Pushalkar S, Hundeyin M, Daley D, Zambirinis CP, Kurz E et al. 2018. The pancreatic cancer microbiome promotes oncogenesis by induction of innate and adaptive immune suppression. Cancer Discov. 8:403–16
    [Google Scholar]
  194. 194. 
    Aykut B, Pushalkar S, Chen R, Li Q, Abengozar R et al. 2019. The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL. Nature 574:264–67
    [Google Scholar]
  195. 195. 
    Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K et al. 2015. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 350:1084–89
    [Google Scholar]
  196. 196. 
    Vétizou M, Pitt JM, Daillère R, Lepage P, Waldschmitt N et al. 2015. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 350:1079–84
    [Google Scholar]
  197. 197. 
    Baruch EN, Youngster I, Ben-Betzalel G, Ortenberg R, Lahat A et al. 2021. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science 371:602–9
    [Google Scholar]
  198. 198. 
    Davar D, Dzutsev AK, McCulloch JA, Rodrigues RR, Chauvin JM et al. 2021. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. Science 371:595–602
    [Google Scholar]
  199. 199. 
    Finotello F, Trajanoski Z. 2018. Quantifying tumor-infiltrating immune cells from transcriptomics data. Cancer Immunol. Immunother. 67:1031–40
    [Google Scholar]
  200. 200. 
    Kim IS, Gao Y, Welte T, Wang H, Liu J et al. 2019. Immuno-subtyping of breast cancer reveals distinct myeloid cell profiles and immunotherapy resistance mechanisms. Nat. Cell Biol. 21:1113–26
    [Google Scholar]
  201. 201. 
    Lavin Y, Kobayashi S, Leader A, Amir ED, Elefant N et al. 2017. Innate immune landscape in early lung adenocarcinoma by paired single-cell analyses. Cell 169:750–65.e17
    [Google Scholar]
  202. 202. 
    Tsujikawa T, Kumar S, Borkar RN, Azimi V, Thibault G et al. 2017. Quantitative multiplex immunohistochemistry reveals myeloid-inflamed tumor-immune complexity associated with poor prognosis. Cell Rep 19:203–17
    [Google Scholar]
  203. 203. 
    Keren L, Bosse M, Marquez D, Angoshtari R, Jain S et al. 2018. A structured tumor-immune microenvironment in triple negative breast cancer revealed by multiplexed ion beam imaging. Cell 174:1373–87.e19
    [Google Scholar]
  204. 204. 
    Gruosso T, Gigoux M, Manem VSK, Bertos N et al. 2019. Spatially distinct tumor immune microenvironments stratify triple-negative breast cancers. J. Clin. Investig. 129:1785–800
    [Google Scholar]
  205. 205. 
    Rozenblatt-Rosen O, Regev A, Oberdoerffer P, Nawy T, Hupalowska A et al. 2020. The Human Tumor Atlas Network: charting tumor transitions across space and time at single-cell resolution. Cell 181:236–49
    [Google Scholar]
  206. 206. 
    Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA et al. 2010. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363:711–23
    [Google Scholar]
  207. 207. 
    van Puffelen JH, Keating ST, Oosterwijk E, van der Heijden AG, Netea MG et al. 2020. Trained immunity as a molecular mechanism for BCG immunotherapy in bladder cancer. Nat. Rev. Urol. 17:513–25
    [Google Scholar]
  208. 208. 
    Kubota Y, Takubo K, Shimizu T, Ohno H, Kishi K et al. 2009. M-CSF inhibition selectively targets pathological angiogenesis and lymphangiogenesis. J. Exp. Med. 206:1089–102
    [Google Scholar]
  209. 209. 
    Li M, Knight DA, Snyder LA, Smyth MJ, Stewart TJ. 2013. A role for CCL2 in both tumor progression and immunosurveillance. Oncoimmunology 2:e25474
    [Google Scholar]
  210. 210. 
    Pienta KJ, Machiels JP, Schrijvers D, Alekseev B, Shkolnik M et al. 2013. Phase 2 study of carlumab (CNTO 888), a human monoclonal antibody against CC-chemokine ligand 2 (CCL2), in metastatic castration-resistant prostate cancer. Investig. New Drugs 31:760–68
    [Google Scholar]
  211. 211. 
    Nywening TM, Wang-Gillam A, Sanford DE, Belt BA, Panni RZ et al. 2016. Targeting tumour-associated macrophages with CCR2 inhibition in combination with FOLFIRINOX in patients with borderline resectable and locally advanced pancreatic cancer: a single-centre, open-label, dose-finding, non-randomised, phase 1b trial. Lancet Oncol. 17:651–62
    [Google Scholar]
  212. 212. 
    Tap WD, Wainberg ZA, Anthony SP, Ibrahim PN, Zhang C et al. 2015. Structure-guided blockade of CSF1R kinase in tenosynovial giant-cell tumor. N. Engl. J. Med. 373:428–37
    [Google Scholar]
  213. 213. 
    Butowski N, Colman H, De Groot JF, Omuro AM, Nayak L et al. 2016. Orally administered colony stimulating factor 1 receptor inhibitor PLX3397 in recurrent glioblastoma: an Ivy Foundation Early Phase Clinical Trials Consortium phase II study. Neuro-Oncology 18:557–64
    [Google Scholar]
  214. 214. 
    Cassier PA, Italiano A, Gomez-Roca CA, Le Tourneau C, Toulmonde M et al. 2015. CSF1R inhibition with emactuzumab in locally advanced diffuse-type tenosynovial giant cell tumours of the soft tissue: a dose-escalation and dose-expansion phase 1 study. Lancet Oncol. 16:949–56
    [Google Scholar]
  215. 215. 
    Razak AR, Cleary JM, Moreno V, Boyer M, Calvo Aller E et al. 2020. Safety and efficacy of AMG 820, an anti-colony-stimulating factor 1 receptor antibody, in combination with pembrolizumab in adults with advanced solid tumors. J. Immunother. Cancer 8:e001006
    [Google Scholar]
  216. 216. 
    Kaczanowska S, Beury DW, Gopalan V, Tycko AK, Qin H et al. 2021. Genetically engineered myeloid cells rebalance the core immune-suppression program in metastasis. Cell 184:82033–52.e21
    [Google Scholar]
  217. 217. 
    Aleynick M, Svensson-Arvelund J, Flowers CR, Marabelle A, Brody JD. 2019. Pathogen molecular pattern receptor agonists: treating cancer by mimicking infection. Clin. Cancer Res. 25:6283–94
    [Google Scholar]
  218. 218. 
    Smith M, García-Martínez E, Pitter MR, Fucikova J, Spisek R et al. 2018. Trial Watch: Toll-like receptor agonists in cancer immunotherapy. Oncoimmunology 7:e1526250
    [Google Scholar]
  219. 219. 
    Adams S, Kozhaya L, Martiniuk F, Meng TC, Chiriboga L et al. 2012. Topical TLR7 agonist imiquimod can induce immune-mediated rejection of skin metastases in patients with breast cancer. Clin. Cancer Res. 18:6748–57
    [Google Scholar]
  220. 220. 
    Smith DA, Conkling P, Richards DA, Nemunaitis JJ, Boyd TE et al. 2014. Antitumor activity and safety of combination therapy with the Toll-like receptor 9 agonist IMO-2055, erlotinib, and bevacizumab in advanced or metastatic non-small cell lung cancer patients who have progressed following chemotherapy. Cancer Immunol. Immunother. 63:787–96
    [Google Scholar]
  221. 221. 
    Dietsch GN. 2016. Motolimod effectively drives immune activation in advanced cancer patients. Oncoimmunology 5:e1126037
    [Google Scholar]
  222. 222. 
    Na YR, Yoon YN, Son D, Jung D, Gu GJ, Seok SH 2015. Consistent inhibition of cyclooxygenase drives macrophages towards the inflammatory phenotype. PLOS ONE 10:e0118203
    [Google Scholar]
  223. 223. 
    Nakanishi Y, Nakatsuji M, Seno H, Ishizu S, Akitake-Kawano R et al. 2011. COX-2 inhibition alters the phenotype of tumor-associated macrophages from M2 to M1 in ApcMin/+ mouse polyps. Carcinogenesis 32:1333–39
    [Google Scholar]
  224. 224. 
    Lin J-Z, Hameed I, Xu Z, Yu Y, Ren Z-Y, Zhu JG. 2018. Efficacy of gefitinib-celecoxib combination therapy in docetaxel-resistant prostate cancer. Oncol. Rep. 40:2242–50
    [Google Scholar]
  225. 225. 
    Guerriero JL, Sotayo A, Ponichtera HE, Castrillon JA, Pourzia AL et al. 2017. Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages. Nature 543:428–32
    [Google Scholar]
  226. 226. 
    Kaneda MM, Messer KS, Ralainirina N, Li H, Leem CJ et al. 2016. PI3Kγ is a molecular switch that controls immune suppression. Nature 539:437–42
    [Google Scholar]
  227. 227. 
    Downey CM, Aghaei M, Schwendener RA, Jirik FR. 2014. DMXAA causes tumor site-specific vascular disruption in murine non-small cell lung cancer, and like the endogenous non-canonical cyclic dinucleotide STING agonist, 2′3′-cGAMP, induces M2 macrophage repolarization. PLOS ONE 9:e99988
    [Google Scholar]
  228. 228. 
    Li A, Yi M, Qin S, Song Y, Chu Q, Wu K 2019. Activating cGAS-STING pathway for the optimal effect of cancer immunotherapy. J. Hematol. Oncol. 12:35
    [Google Scholar]
  229. 229. 
    Anguille S, Smits EL, Bryant C, Van Acker HH, Goossens H et al. 2015. Dendritic cells as pharmacological tools for cancer immunotherapy. Pharmacol. Rev. 67:731–53
    [Google Scholar]
  230. 230. 
    Dhodapkar MV, Steinman RM, Krasovsky J, Munz C, Bhardwaj N. 2001. Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J. Exp. Med. 193:233–38
    [Google Scholar]
  231. 231. 
    Kim JH, Kang TH, Noh KH, Kim S-H, Lee Y-H et al. 2010. Enhancement of DC vaccine potency by activating the PI3K/AKT pathway with a small interfering RNA targeting PTEN. Immunol. Lett. 134:47–54
    [Google Scholar]
  232. 232. 
    Theisen DJ, Davidson JT4th, Briseno CG, Gargaro M, Lauron EJ et al. 2018. WDFY4 is required for cross-presentation in response to viral and tumor antigens. Science 362:694–99
    [Google Scholar]
  233. 233. 
    Handy CE, Antonarakis ES. 2018. Sipuleucel-T for the treatment of prostate cancer: novel insights and future directions. Future Oncol. 14:907–17
    [Google Scholar]
  234. 234. 
    Schreibelt G, Bol KF, Westdorp H, Wimmers F, Aarntzen EH et al. 2016. Effective clinical responses in metastatic melanoma patients after vaccination with primary myeloid dendritic cells. Clin. Cancer Res. 22:2155–66
    [Google Scholar]
  235. 235. 
    Hammerich L, Marron TU, Upadhyay R, Svensson-Arvelund J, Dhainaut M et al. 2019. Systemic clinical tumor regressions and potentiation of PD1 blockade with in situ vaccination. Nat. Med. 25:814–24
    [Google Scholar]
  236. 236. 
    Van Lint S, Renmans D, Broos K, Goethals L, Maenhout S et al. 2016. Intratumoral delivery of TriMix mRNA results in T-cell activation by cross-presenting dendritic cells. Cancer Immunol. Res. 4:146–56
    [Google Scholar]
  237. 237. 
    Ylosmaki E, Cerullo V 2020. Design and application of oncolytic viruses for cancer immunotherapy. Curr. Opin. Biotechnol. 65:25–36
    [Google Scholar]
  238. 238. 
    Li Y, Su Z, Zhao W, Zhang X, Momin N, Zhang C et al. 2020. Multifunctional oncolytic nanoparticles deliver self-replicating IL-12 RNA to eliminate established tumors and prime systemic immunity. Nat. Cancer 1:882–93
    [Google Scholar]
  239. 239. 
    Khalil DN, Suek N, Campesato LF, Budhu S, Redmond D et al. 2019. In situ vaccination with defined factors overcomes T cell exhaustion in distant tumors. J. Clin. Investig. 129:3435–47
    [Google Scholar]
  240. 240. 
    Corrales L, Glickman LH, McWhirter SM, Kanne DB, Sivick KE et al. 2015. Direct activation of STING in the tumor microenvironment leads to potent and systemic tumor regression and immunity. Cell Rep. 11:1018–30
    [Google Scholar]
  241. 241. 
    Muntasell A, Ochoa MC, Cordeiro L, Berraondo P, López-Díaz de Cerio A et al. 2017. Targeting NK-cell checkpoints for cancer immunotherapy. Curr. Opin. Immunol. 45:73–81
    [Google Scholar]
  242. 242. 
    Amin A, White RL Jr. 2013. High-dose interleukin-2: Is it still indicated for melanoma and RCC in an era of targeted therapies?. Oncology 27:680–91
    [Google Scholar]
  243. 243. 
    Romagné F, André P, Spee P, Zahn S, Anfossi N et al. 2009. Preclinical characterization of 1-7F9, a novel human anti-KIR receptor therapeutic antibody that augments natural killer-mediated killing of tumor cells. Blood 114:2667–77
    [Google Scholar]
  244. 244. 
    Mamessier E, Sylvain A, Thibult ML, Houvenaeghel G, Jacquemier J et al. 2011. Human breast cancer cells enhance self tolerance by promoting evasion from NK cell antitumor immunity. J. Clin. Investig. 121:3609–22
    [Google Scholar]
  245. 245. 
    van Hall T, Andre P, Horowitz A, Ruan DF, Borst L et al. 2019. Monalizumab: inhibiting the novel immune checkpoint NKG2A. J. Immunother. Cancer 7:263
    [Google Scholar]
  246. 246. 
    Rothe A, Sasse S, Topp MS, Eichenauer DA, Hummel H et al. 2015. A phase 1 study of the bispecific anti-CD30/CD16A antibody construct AFM13 in patients with relapsed or refractory Hodgkin lymphoma. Blood 125:4024–31
    [Google Scholar]
  247. 247. 
    Vallera DA, Felices M, McElmurry R, McCullar V, Zhou X et al. 2016. IL15 trispecific killer engagers (TriKE) make natural killer cells specific to CD33+ targets while also inducing persistence, in vivo expansion, and enhanced function. Clin Cancer Res 22:3440–50
    [Google Scholar]
  248. 248. 
    Lin C, Zhang J 2018. Reformation in chimeric antigen receptor based cancer immunotherapy: redirecting natural killer cell. Biochim. Biophys. Acta Rev. Cancer 1869:200–15
    [Google Scholar]
  249. 249. 
    Liu E, Marin D, Banerjee P, Macapinlac HA, Thompson P et al. 2020. Use of CAR-transduced natural killer cells in CD19-positive lymphoid tumors. N. Engl. J. Med. 382:545–53
    [Google Scholar]
  250. 250. 
    Martin C, Burdon PC, Bridger G, Gutierrez-Ramos JC, Williams TJ, Rankin SM 2003. Chemokines acting via CXCR2 and CXCR4 control the release of neutrophils from the bone marrow and their return following senescence. Immunity 19:583–93
    [Google Scholar]
  251. 251. 
    Schott AF, Goldstein LJ, Cristofanilli M, Ruffini PA, McCanna S et al. 2017. Phase Ib pilot study to evaluate reparixin in combination with weekly paclitaxel in patients with HER-2–negative metastatic breast cancer. Clin. Cancer Res. 23:5358–65
    [Google Scholar]
  252. 252. 
    Steggerda SM, Bennett MK, Chen J, Emberley E, Huang T et al. 2017. Inhibition of arginase by CB-1158 blocks myeloid cell-mediated immune suppression in the tumor microenvironment. J. Immunother. Cancer 5:101
    [Google Scholar]
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