1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Pharmacology and Toxicology
  4. Volume 65, 2025
  5. Article

Annual Review of Pharmacology and Toxicology

Volume 65, 2025

Gut Microbiota–Related Biomarkers in Immuno-Oncology

Abstract

Carcinogenesis is associated with the emergence of protracted intestinal dysbiosis and metabolic changes. Increasing evidence shows that gut microbiota–related biomarkers and microbiota-centered interventions are promising strategies to overcome resistance to immunotherapy. However, current standard methods for evaluating gut microbiota composition are cost- and time-consuming. The development of routine diagnostic tools for intestinal barrier alterations and dysbiosis constitutes a critical unmet medical need that can guide routine treatment and microbiota-centered intervention decisions in patients with cancer. In this review, we explore the influence of gut microbiota on cancer immunotherapy and highlight gut-associated biomarkers that have the potential to be transformed into simple diagnostic tools, thus guiding standard treatment decisions in the field of immuno-oncology. Mechanistic insights toward leveraging the complex relationship between cancer immunosurveillance, gut microbiota, and metabolism open exciting opportunities for developing novel biomarkers in immuno-oncology.

Keyword(s): biomarkers, cancer, gut, immuno-oncology, immunotherapy, microbiota
Loading

Article metrics loading...

/content/journals/10.1146/annurev-pharmtox-061124-102218
2025-01-23
2025-04-30
Loading full text...

Full text loading...

/deliver/fulltext/pharmtox/65/1/annurev-pharmtox-061124-102218.html?itemId=/content/journals/10.1146/annurev-pharmtox-061124-102218&mimeType=html&fmt=ahah

Literature Cited

  1. 1.
    Bray F, Laversanne M, Weiderpass E, Soerjomataram I. 2021.. The ever-increasing importance of cancer as a leading cause of premature death worldwide. . Cancer 127:(16):3029–30
     [Crossref] [Google Scholar]
  2. 2.
    Zhao J, Xu L, Sun J, Song M, Wang L, et al. 2023.. Global trends in incidence, death, burden and risk factors of early-onset cancer from 1990 to 2019. . BMJ Oncol. 2:(1):e000049
     [Crossref] [Google Scholar]
  3. 3.
    Wu Q, Qian W, Sun X, Jiang S. 2022.. Small-molecule inhibitors, immune checkpoint inhibitors, and more: FDA-approved novel therapeutic drugs for solid tumors from 1991 to 2021. . J. Hematol. Oncol. 15:(1):143
     [Crossref] [Google Scholar]
  4. 4.
    Chen DS, Mellman I. 2017.. Elements of cancer immunity and the cancer-immune set point. . Nature 541:(7637):321–30
     [Crossref] [Google Scholar]
  5. 5.
    De Visser KE, Joyce JA. 2023.. The evolving tumor microenvironment: from cancer initiation to metastatic outgrowth. . Cancer Cell 41:(3):374–403
     [Crossref] [Google Scholar]
  6. 6.
    Hanahan D. 2022.. Hallmarks of cancer: new dimensions. . Cancer Discov. 12:(1):31–46
     [Crossref] [Google Scholar]
  7. 7.
    Derosa L, Routy B, Desilets A, Daillère R, Terrisse S, et al. 2021.. Microbiota-centered interventions: the next breakthrough in immuno-oncology?. Cancer Discov. 11:(10):2396–412
     [Crossref] [Google Scholar]
  8. 8.
    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:(6529):602–9
     [Crossref] [Google Scholar]
  9. 9.
    Davar D, Dzutsev AK, McCulloch JA, Rodrigues RR, Chauvin J-M, et al. 2021.. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. . Science 371:(6529):595–602
     [Crossref] [Google Scholar]
  10. 10.
    Routy B, Lenehan JG, Miller WH, Jamal R, Messaoudene M, et al. 2023.. Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial. . Nat. Med. 29:(8):2121–32
     [Crossref] [Google Scholar]
  11. 11.
    Dizman N, Meza L, Bergerot P, Alcantara M, Dorff T, et al. 2022.. Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial. . Nat. Med. 28:(4):704–12
     [Crossref] [Google Scholar]
  12. 12.
    Ebrahimi H, Meza LA, Lee K, Malhotra J, Alcantara M, et al. 2023.. Effect of CBM588 in combination with cabozantinib plus nivolumab for patients (pts) with metastatic renal cell carcinoma (mRCC): a randomized clinical trial. . J. Clin. Oncol. 41:(17_Suppl.):LBA104
     [Crossref] [Google Scholar]
  13. 13.
    Donaldson GP, Lee SM, Mazmanian SK. 2016.. Gut biogeography of the bacterial microbiota. . Nat. Rev. Microbiol. 14:(1):20–32
     [Crossref] [Google Scholar]
  14. 14.
    Sender R, Fuchs S, Milo R. 2016.. Revised estimates for the number of human and bacteria cells in the body. . PLOS Biol. 14:(8):e1002533
     [Crossref] [Google Scholar]
  15. 15.
    Forster SC, Kumar N, Anonye BO, Almeida A, Viciani E, et al. 2019.. A human gut bacterial genome and culture collection for improved metagenomic analyses. . Nat. Biotechnol. 37:(2):186–92
     [Crossref] [Google Scholar]
  16. 16.
    Dethlefsen L, McFall-Ngai M, Relman DA. 2007.. An ecological and evolutionary perspective on human-microbe mutualism and disease. . Nature 449:(7164):811–18
     [Crossref] [Google Scholar]
  17. 17.
    Senghor B, Sokhna C, Ruimy R, Lagier J-C. 2018.. Gut microbiota diversity according to dietary habits and geographical provenance. . Hum. Microbiome J. 7–8::1–9
     [Crossref] [Google Scholar]
  18. 18.
    Kamada N, Seo S-U, Chen GY, Núñez G. 2013.. Role of the gut microbiota in immunity and inflammatory disease. . Nat. Rev. Immunol. 13:(5):321–35
     [Crossref] [Google Scholar]
  19. 19.
    Wu H-J, Wu E. 2012.. The role of gut microbiota in immune homeostasis and autoimmunity. . Gut Microbes 3:(1):4–14
     [Crossref] [Google Scholar]
  20. 20.
    Gacesa R, Kurilshikov A, Vich Vila A, Sinha T, Klaassen MAY, et al. 2022.. Environmental factors shaping the gut microbiome in a Dutch population. . Nature 604:(7907):732–39
     [Crossref] [Google Scholar]
  21. 21.
    Rothschild D, Weissbrod O, Barkan E, Kurilshikov A, Korem T, et al. 2018.. Environment dominates over host genetics in shaping human gut microbiota. . Nature 555:(7695):210–15
     [Crossref] [Google Scholar]
  22. 22.
    Song SJ, Lauber C, Costello EK, Lozupone CA, Humphrey G, et al. 2013.. Cohabiting family members share microbiota with one another and with their dogs. . eLife 2::e00458
     [Crossref] [Google Scholar]
  23. 23.
    Xie H, Guo R, Zhong H, Feng Q, Lan Z, et al. 2016.. Shotgun metagenomics of 250 adult twins reveals genetic and environmental impacts on the gut microbiome. . Cell Syst. 3:(6):572–584.e3
     [Crossref] [Google Scholar]
  24. 24.
    Rampelli S, Soverini M, D'Amico F, Barone M, Tavella T, et al. 2020.. Shotgun metagenomics of gut microbiota in humans with up to extreme longevity and the increasing role of xenobiotic degradation. . mSystems 5:(2):e00124-20
     [Crossref] [Google Scholar]
  25. 25.
    Ghosh TS, Das M, Jeffery IB, O'Toole PW. 2020.. Adjusting for age improves identification of gut microbiome alterations in multiple diseases. . eLife 9::e50240
     [Crossref] [Google Scholar]
  26. 26.
    Luan Z, Sun G, Huang Y, Yang Y, Yang R, et al. 2020.. Metagenomics study reveals changes in gut microbiota in centenarians: a cohort study of Hainan centenarians. . Front. Microbiol. 11::1474
     [Crossref] [Google Scholar]
  27. 27.
    Sato Y, Atarashi K, Plichta DR, Arai Y, Sasajima S, et al. 2021.. Novel bile acid biosynthetic pathways are enriched in the microbiome of centenarians. . Nature 599:(7885):458–64
     [Crossref] [Google Scholar]
  28. 28.
    Wang J, Qie J, Zhu D, Zhang X, Zhang Q, et al. 2022.. The landscape in the gut microbiome of long-lived families reveals new insights on longevity and aging—relevant neural and immune function. . Gut Microbes 14:(1):2107288
     [Crossref] [Google Scholar]
  29. 29.
    Wu H, Esteve E, Tremaroli V, Khan MT, Caesar R, et al. 2017.. Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug. . Nat. Med. 23:(7):850–58
     [Crossref] [Google Scholar]
  30. 30.
    Imhann F, Bonder MJ, Vich Vila A, Fu J, Mujagic Z, et al. 2016.. Proton pump inhibitors affect the gut microbiome. . Gut 65:(5):740–48
     [Crossref] [Google Scholar]
  31. 31.
    Derosa L, Routy B, Fidelle M, Iebba V, Alla L, et al. 2020.. Gut bacteria composition drives primary resistance to cancer immunotherapy in renal cell carcinoma patients. . Eur. Urol. 78:(2):195–206
     [Crossref] [Google Scholar]
  32. 32.
    Derosa L, Hellmann MD, Spaziano M, Halpenny D, Fidelle M, et al. 2018.. Negative association of antibiotics on clinical activity of immune checkpoint inhibitors in patients with advanced renal cell and non-small-cell lung cancer. . Ann. Oncol. 29:(6):1437–44
     [Crossref] [Google Scholar]
  33. 33.
    Derosa L, Zitvogel L. 2020.. Antibiotics impair immunotherapy for urothelial cancer. . Nat. Rev. Urol. 17::605–6
     [Crossref] [Google Scholar]
  34. 34.
    Elkrief A, Derosa L, Kroemer G, Zitvogel L, Routy B. 2019.. The negative impact of antibiotics on outcomes in cancer patients treated with immunotherapy: a new independent prognostic factor?. Ann. Oncol. 30:(10):1572–79
     [Crossref] [Google Scholar]
  35. 35.
    Huang X-Z, Gao P, Wang Z-N. 2020.. Antibiotic treatment and immune checkpoint inhibitor therapy in patients with cancer. . JAMA Oncol. 6:(4):586–87
     [Crossref] [Google Scholar]
  36. 36.
    Serpas V, Rogers JE, Xiao L, Mola-Rudd K, Dasari A, et al. 2020.. Impact of antibiotic exposure on the efficacy of immune checkpoint blockade in MSI-H metastatic CRC. . J. Clin. Oncol. 38:(4_Suppl.): 161:
     [Google Scholar]
  37. 37.
    Pinato DJ, Howlett S, Ottaviani D, Urus H, Patel A, et al. 2019.. Association of prior antibiotic treatment with survival and response to immune checkpoint inhibitor therapy in patients with cancer. . JAMA Oncol. 5:(12):1774–78
     [Crossref] [Google Scholar]
  38. 38.
    Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, et al. 2018.. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. . Science 359:(6371):91–97
     [Crossref] [Google Scholar]
  39. 39.
    Peled JU, Gomes ALC, Devlin SM, Littmann ER, Taur Y, et al. 2020.. Microbiota as predictor of mortality in allogeneic hematopoietic-cell transplantation. . N. Engl. J. Med. 382:(9):822–34
     [Crossref] [Google Scholar]
  40. 40.
    Stein-Thoeringer CK, Saini NY, Zamir E, Blumenberg V, Schubert M-L, et al. 2023.. A non-antibiotic-disrupted gut microbiome is associated with clinical responses to CD19-CAR-T cell cancer immunotherapy. . Nat. Med. 29:(4):906–16
     [Crossref] [Google Scholar]
  41. 41.
    Smith M, Dai A, Ghilardi G, Amelsberg KV, Devlin SM, et al. 2022.. Gut microbiome correlates of response and toxicity following anti-CD19 CAR T cell therapy. . Nat. Med. 28:(4):713–23
     [Crossref] [Google Scholar]
  42. 42.
    Zhang Z, Tang H, Chen P, Xie H, Tao Y. 2019.. Demystifying the manipulation of host immunity, metabolism, and extraintestinal tumors by the gut microbiome. . Signal Transduct. Target. Ther. 4:(1):41
     [Crossref] [Google Scholar]
  43. 43.
    Fidelle M, Rauber C, Alves Costa Silva C, Tian A-L, Lahmar I, et al. 2023.. A microbiota-modulated checkpoint directs immunosuppressive intestinal T cells into cancers. . Science 380:(6649):eabo2296
     [Crossref] [Google Scholar]
  44. 44.
    Yonekura S, Terrisse S, Alves Costa Silva C, Lafarge A, Iebba V, et al. 2022.. Cancer induces a stress ileopathy depending on β-adrenergic receptors and promoting dysbiosis that contributes to carcinogenesis. . Cancer Discov. 12:(4):1128–51
     [Crossref] [Google Scholar]
  45. 45.
    Briskin M, Winsor-Hines D, Shyjan A, Cochran N, Bloom S, et al. 1997.. Human mucosal addressin cell adhesion molecule-1 is preferentially expressed in intestinal tract and associated lymphoid tissue. . Am. J. Pathol. 151:(1):97–110
     [Google Scholar]
  46. 46.
    Choi Y, Lichterman JN, Coughlin LA, Poulides N, Li W, et al. 2023.. Immune checkpoint blockade induces gut microbiota translocation that augments extraintestinal antitumor immunity. . Sci. Immunol. 8:(81):eabo2003
     [Crossref] [Google Scholar]
  47. 47.
    Li Y, Tinoco R, Elmén L, Segota I, Xian Y, et al. 2019.. Gut microbiota dependent anti-tumor immunity restricts melanoma growth in Rnf5−/− mice. . Nat. Commun. 10:(1):1492
     [Crossref] [Google Scholar]
  48. 48.
    Le Chatelier E, Nielsen T, Qin J, Prifti E, Hildebrand F, et al. 2013.. Richness of human gut microbiome correlates with metabolic markers. . Nature 500:(7464):541–46
     [Crossref] [Google Scholar]
  49. 49.
    Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, et al. 2018.. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. . Science 359:(6371):97–103
     [Crossref] [Google Scholar]
  50. 50.
    Viaud S, Saccheri F, Mignot G, Yamazaki T, Daillere R, et al. 2013.. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. . Science 342:(6161):971–76
     [Crossref] [Google Scholar]
  51. 51.
    Vetizou M, Pitt JM, Daillere R, Lepage P, Waldschmitt N, et al. 2015.. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. . Science 350:(6264):1079–84
     [Crossref] [Google Scholar]
  52. 52.
    Routy B, Gopalakrishnan V, Daillère R, Zitvogel L, Wargo JA, Kroemer G. 2018.. The gut microbiota influences anticancer immunosurveillance and general health. . Nat. Rev. Clin. Oncol. 15:(6):382–96
     [Crossref] [Google Scholar]
  53. 53.
    Tanoue T, Morita S, Plichta DR, Skelly AN, Suda W, et al. 2019.. A defined commensal consortium elicits CD8 T cells and anti-cancer immunity. . Nature 565:(7741):600–5
     [Crossref] [Google Scholar]
  54. 54.
    Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, et al. 2018.. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. . Science 359:(6371):104–8
     [Crossref] [Google Scholar]
  55. 55.
    Thomas AM, Fidelle M, Routy B, Kroemer G, Wargo JA, et al. 2023.. Gut OncoMicrobiome Signatures (GOMS) as next-generation biomarkers for cancer immunotherapy. . Nat. Rev. Clin. Oncol. 20::583–603
     [Crossref] [Google Scholar]
  56. 56.
    McCulloch JA, Davar D, Rodrigues RR, Badger JH, Fang JR, et al. 2022.. Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1. . Nat. Med. 28:(3):545–56
     [Crossref] [Google Scholar]
  57. 57.
    Alves Costa Silva C, Piccinno G, Cerbone L, Iebba V, Colomba E, et al. 2022.. Longitudinal analysis reveals gut microbiota shift during standard therapies in metastatic renal cell carcinoma (mRCC). . Ann. Oncol. 33::1452MO
     [Crossref] [Google Scholar]
  58. 58.
    Park EM, Chelvanambi M, Bhutiani N, Kroemer G, Zitvogel L, Wargo JA. 2022.. Targeting the gut and tumor microbiota in cancer. . Nat. Med. 28:(4):690–703
     [Crossref] [Google Scholar]
  59. 59.
    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:(6264):1084–89
     [Crossref] [Google Scholar]
  60. 60.
    Cardona S, Eck A, Cassellas M, Gallart M, Alastrue C, et al. 2012.. Storage conditions of intestinal microbiota matter in metagenomic analysis. . BMC Microbiol. 12:(1):158
     [Crossref] [Google Scholar]
  61. 61.
    Derosa L, Routy B, Thomas AM, Iebba V, Zalcman G, et al. 2022.. Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer. . Nat. Med. 28:(2):315–24
     [Crossref] [Google Scholar]
  62. 62.
    Frankel AE, Coughlin LA, Kim J, Froehlich TW, Xie Y, et al. 2017.. Metagenomic shotgun sequencing and unbiased metabolomic profiling identify specific human gut microbiota and metabolites associated with immune checkpoint therapy efficacy in melanoma patients. . Neoplasia 19:(10):848–55
     [Crossref] [Google Scholar]
  63. 63.
    Chaput N, Lepage P, Coutzac C, Soularue E, Le Roux K, et al. 2017.. Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab. . Ann. Oncol. 28:(6):1368–79
     [Crossref] [Google Scholar]
  64. 64.
    Alves Costa Silva C, Piccinno G, Suissa D, Bourgin M, Schreibelt G, et al. 2024.. Influence of microbiota-associated metabolic reprogramming on clinical outcome in patients with melanoma from the randomized adjuvant dendritic cell-based MIND-DC trial. . Nat. Commun. 15:(1):1633
     [Crossref] [Google Scholar]
  65. 65.
    Iadsee N, Chuaypen N, Techawiwattanaboon T, Jinato T, Patcharatrakul T, et al. 2023.. Identification of a novel gut microbiota signature associated with colorectal cancer in Thai population. . Sci. Rep. 13:(1):6702
     [Crossref] [Google Scholar]
  66. 66.
    Roberti MP, Yonekura S, Duong CPM, Picard M, Ferrere G, et al. 2020.. Chemotherapy-induced ileal crypt apoptosis and the ileal microbiome shape immunosurveillance and prognosis of proximal colon cancer. . Nat. Med. 26:(6):919–31
     [Crossref] [Google Scholar]
  67. 67.
    Almonte AA, Rangarajan H, Yip D, Fahrer AM. 2021.. How does the gut microbiome influence immune checkpoint blockade therapy?. Immunol. Cell Biol. 99:(4):361–72
     [Crossref] [Google Scholar]
  68. 68.
    Derosa L, Iebba V, Alves Costa Silva C, Piccinno G, Wu G, et al. 2024.. Custom scoring based on ecological topology of gut microbiota associated with cancer immunotherapy outcome. . Cell 187:(13):3373–89.E16
     [Crossref] [Google Scholar]
  69. 69.
    Gupta VK, Kim M, Bakshi U, Cunningham KY, Davis JM, et al. 2020.. A predictive index for health status using species-level gut microbiome profiling. . Nat. Commun. 11:(1):4635
     [Crossref] [Google Scholar]
  70. 70.
    Nguyen SM, Tran HTT, Long J, Shrubsole MJ, Cai H, et al. 2024.. Gut microbiome of patients with breast cancer in Vietnam. . J. Clin. Oncol. Glob. Oncol. 10::e2300234
     [Crossref] [Google Scholar]
  71. 71.
    Boulate D, Fidelle M, Caramella C, Issard J, Planché O, et al. 2022.. Epidemiological study to assess the prevalence of lung cancer in patients with smoking-associated atherosclerotic cardiovascular diseases: PREVALUNG study protocol. . BMJ Open 12:(12):e067191
     [Crossref] [Google Scholar]
  72. 72.
    Ghosh P, Swanson L, Sayed IM, Mittal Y, Lim BB, et al. 2020.. The stress polarity signaling (SPS) pathway serves as a marker and a target in the leaky gut barrier: implications in aging and cancer. . Life Sci. Alliance 3:(3):e201900481
     [Crossref] [Google Scholar]
  73. 73.
    Aznar N, Patel A, Rohena CC, Dunkel Y, Joosen LP, et al. 2016.. AMP-activated protein kinase fortifies epithelial tight junctions during energetic stress via its effector GIV/Girdin. . eLife 5::e20795
     [Crossref] [Google Scholar]
  74. 74.
    Shin N-R, Lee J-C, Lee H-Y, Kim M-S, Whon TW, et al. 2014.. An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice. . Gut 63:(5):727–35
     [Crossref] [Google Scholar]
  75. 75.
    Takata F, Dohgu S, Matsumoto J, Machida T, Kaneshima S, et al. 2013.. Metformin induces up-regulation of blood-brain barrier functions by activating AMP-activated protein kinase in rat brain microvascular endothelial cells. . Biochem. Biophys. Res. Commun. 433:(4):586–90
     [Crossref] [Google Scholar]
  76. 76.
    Ducarouge B, Pelissier-Rota M, Lainé M, Cristina N, Vachez Y, et al. 2013.. CRF2 signaling is a novel regulator of cellular adhesion and migration in colorectal cancer cells. . PLOS ONE 8:(11):e79335
     [Crossref] [Google Scholar]
  77. 77.
    Piton G, Capellier G. 2016.. Biomarkers of gut barrier failure in the ICU. . Curr. Opin. Crit. Care 22:(2):152–60
     [Google Scholar]
  78. 78.
    Woo S-H, Lee S-H, Park J-W, Go D-M, Kim D-Y. 2019.. Osteopontin protects colonic mucosa from dextran sodium sulfate-induced acute colitis in mice by regulating junctional distribution of occludin. . Dig. Dis. Sci. 64:(2):421–31
     [Crossref] [Google Scholar]
  79. 79.
    Tabung FK, Birmann BM, Epstein MM, Martínez-Maza O, Breen EC, et al. 2017.. Influence of dietary patterns on plasma soluble CD14, a surrogate marker of gut barrier dysfunction. . Curr. Dev. Nutr. 1:(11):e001396
     [Crossref] [Google Scholar]
  80. 80.
    Lewis JD. 2011.. The utility of biomarkers in the diagnosis and therapy of inflammatory bowel disease. . Gastroenterology 140:(6):1817–26.e2
     [Crossref] [Google Scholar]
  81. 81.
    Genua F, Holý P, Souček P, Liška V, Hughes DJ. 2023.. Association of circulating markers of gut barrier damage and inflammation with colorectal neoplasia stage. . Cancer Res. 83:(7_Suppl.):5544
     [Crossref] [Google Scholar]
  82. 82.
    Keane JM, Las Heras V, Pinheiro J, FitzGerald JA, Núñez-Sánchez MA, et al. 2023.. Akkermansia muciniphila reduces susceptibility to Listeria monocytogenes infection in mice fed a high-fat diet. . Gut Microbes 15:(1):2229948
     [Crossref] [Google Scholar]
  83. 83.
    Nasiri G, Azimirad M, Goudarzi H, Amirkamali S, Yadegar A, et al. 2024.. The inhibitory effects of live and UV-killed Akkermansia muciniphila and its derivatives on cytotoxicity and inflammatory response induced by Clostridioides difficile RT001 in vitro. . Int. Microbiol. 27:(2):393–409
     [Crossref] [Google Scholar]
  84. 84.
    Petrick JL, Florio AA, Zen J, Wang Y, Gewirtz AT, et al. 2023.. Biomarkers of gut barrier dysfunction and risk of hepatocellular carcinoma in the REVEAL-HBV and REVEAL-HCV cohort studies. . Int. J. Cancer 153:(1):44–53
     [Crossref] [Google Scholar]
  85. 85.
    Chen L, Reynolds C, David R, Peace Brewer A. 2020.. Development of an index score for intestinal inflammation-associated dysbiosis using real-world stool test results. . Dig. Dis. Sci. 65:(4):1111–24
     [Crossref] [Google Scholar]
  86. 86.
    Sachpekidis C, Stein-Thoeringer CK, Kopp-Schneider A, Weru V, Dimitrakopoulou-Strauss A, Hassel JC. 2023.. Can physiologic colonic [18F]FDG uptake in PET/CT imaging predict response to immunotherapy in metastatic melanoma?. Eur. J. Nucl. Med. Mol. Imaging 50:(12):3709–22
     [Crossref] [Google Scholar]
  87. 87.
    Sorribas M, Jakob MO, Yilmaz B, Li H, Stutz D, et al. 2019.. FXR modulates the gut-vascular barrier by regulating the entry sites for bacterial translocation in experimental cirrhosis. . J. Hepatol. 71:(6):1126–40
     [Crossref] [Google Scholar]
  88. 88.
    Stan RV, Tse D, Deharvengt SJ, Smits NC, Xu Y, et al. 2012.. The diaphragms of fenestrated endothelia: gatekeepers of vascular permeability and blood composition. . Dev. Cell 23:(6):1203–18
     [Crossref] [Google Scholar]
  89. 89.
    Bertocchi A, Carloni S, Ravenda PS, Bertalot G, Spadoni I, et al. 2021.. Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver. . Cancer Cell 39:(5):708–24.e11
     [Crossref] [Google Scholar]
  90. 90.
    Alves Costa Silva C, Fidelle M, Birebent R, Dalban C, Zoppi S, et al. 2023.. Serum soluble MAdCAM-1: a new biomarker for cancer immunotherapy. . J. Clin. Oncol. 41:(16_Suppl.):4548
     [Crossref] [Google Scholar]
  91. 91.
    Abdel Sater AH, Bouferraa Y, Amhaz G, Haibe Y, Shamseddine A. 2022.. From tumor cells to endothelium and gut microbiome: a complex interaction favoring the metastasis cascade. . Front. Oncol. 12::804983
     [Crossref] [Google Scholar]
  92. 92.
    Banerjee S, Wei Z, Tian T, Bose D, Shih NNC, et al. 2021.. Prognostic correlations with the microbiome of breast cancer subtypes. . Cell Death Dis. 12:(9):831
     [Crossref] [Google Scholar]
  93. 93.
    Dohlman AB, Klug J, Mesko M, Gao IH, Lipkin SM, et al. 2022.. A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors. . Cell 185:(20):3807–22.e12
     [Crossref] [Google Scholar]
  94. 94.
    Goubet A-G. 2023.. Could the tumor-associated microbiota be the new multi-faceted player in the tumor microenvironment?. Front. Oncol. 13::1185163
     [Crossref] [Google Scholar]
  95. 95.
    Narunsky-Haziza L, Sepich-Poore GD, Livyatan I, Asraf O, Martino C, et al. 2022.. Pan-cancer analyses reveal cancer-type-specific fungal ecologies and bacteriome interactions. . Cell 185:(20):3789–806.e17
     [Crossref] [Google Scholar]
  96. 96.
    Tzeng A, Sangwan N, Jia M, Liu C-C, Keslar KS, et al. 2021.. Human breast microbiome correlates with prognostic features and immunological signatures in breast cancer. . Genome Med. 13:(1):60
     [Crossref] [Google Scholar]
  97. 97.
    Nejman D, Livyatan I, Fuks G, Gavert N, Zwang Y, et al. 2020.. The human tumor microbiome is composed of tumor type-specific intracellular bacteria. . Science 368:(6494):973–80
     [Crossref] [Google Scholar]
  98. 98.
    Farias A, Soto A, Puttur F, Goldin CJ, Sosa S, et al. 2021.. A TLR4 agonist improves immune checkpoint blockade treatment by increasing the ratio of effector to regulatory cells within the tumor microenvironment. . Sci. Rep. 11:(1):15406
     [Crossref] [Google Scholar]
  99. 99.
    Sharma N, Vacher J, Allison JP. 2019.. TLR1/2 ligand enhances antitumor efficacy of CTLA-4 blockade by increasing intratumoral Treg depletion. . PNAS 116:(21):10453–62
     [Crossref] [Google Scholar]
  100. 100.
    Postow MA, Sidlow R, Hellmann MD. 2018.. Immune-related adverse events associated with immune checkpoint blockade. . N. Engl. J. Med. 378:(2):158–68
     [Crossref] [Google Scholar]
  101. 101.
    Dougan M. 2023.. Gastrointestinal mucosal toxicities from immune checkpoint inhibitors: current understanding and future directions. . Immunol. Rev. 318:(1):11–21
     [Crossref] [Google Scholar]
  102. 102.
    Soularue E, Lepage P, Colombel JF, Coutzac C, Faleck D, et al. 2018.. Enterocolitis due to immune checkpoint inhibitors: a systematic review. . Gut 67:(11):2056–67
     [Crossref] [Google Scholar]
  103. 103.
    Ye W, Olsson-Brown A, Watson RA, Cheung VTF, Morgan RD, et al. 2021.. Checkpoint-blocker-induced autoimmunity is associated with favourable outcome in metastatic melanoma and distinct T-cell expression profiles. . Br. J. Cancer 124:(10):1661–69
     [Crossref] [Google Scholar]
  104. 104.
    Naghavian R, Faigle W, Oldrati P, Wang J, Toussaint NC, et al. 2023.. Microbial peptides activate tumour-infiltrating lymphocytes in glioblastoma. . Nature 617:(7962):807–17
     [Crossref] [Google Scholar]
  105. 105.
    Ragone C, Manolio C, Mauriello A, Cavalluzzo B, Buonaguro FM, et al. 2022.. Molecular mimicry between tumor associated antigens and microbiota-derived epitopes. . J. Transl. Med. 20:(1):316
     [Crossref] [Google Scholar]
  106. 106.
    Zitvogel L, Kroemer G. 2022.. Cross-reactivity between microbial and tumor antigens. . Curr. Opin. Immunol. 75::102171
     [Crossref] [Google Scholar]
  107. 107.
    Fluckiger A, Daillère R, Sassi M, Sixt BS, Liu P, et al. 2020.. Cross-reactivity between tumor MHC class I-restricted antigens and an enterococcal bacteriophage. . Science 369:(6506):936–42
     [Crossref] [Google Scholar]
  108. 108.
    Kalaora S, Nagler A, Nejman D, Alon M, Barbolin C, et al. 2021.. Identification of bacteria-derived HLA-bound peptides in melanoma. . Nature 592:(7852):138–43
     [Crossref] [Google Scholar]
  109. 109.
    Cui C, Wang J, Fagerberg E, Chen P-M, Connolly KA, et al. 2021.. Neoantigen-driven B cell and CD4 T follicular helper cell collaboration promotes anti-tumor CD8 T cell responses. . Cell 184:(25):6101–18.e13
     [Crossref] [Google Scholar]
  110. 110.
    Ng KW, Boumelha J, Enfield KSS, Almagro J, Cha H, et al. 2023.. Antibodies against endogenous retroviruses promote lung cancer immunotherapy. . Nature 616:(7957):563–73
     [Crossref] [Google Scholar]
  111. 111.
    Goubet A-G, Lordello L, Alves Costa Silva C, Peguillet I, Gazzano M, et al. 2022.. Escherichia coli-specific CXCL13-producing TFH are associated with clinical efficacy of neoadjuvant PD-1 blockade against muscle-invasive bladder cancer. . Cancer Discov. 12:(10):2280–307
     [Crossref] [Google Scholar]
  112. 112.
    Jones GW, Hill DG, Jones SA. 2016.. Understanding immune cells in tertiary lymphoid organ development: It is all starting to come together. . Front. Immunol. 7::401
     [Crossref] [Google Scholar]
  113. 113.
    Sautès-Fridman C, Lawand M, Giraldo NA, Kaplon H, Germain C, et al. 2016.. Tertiary lymphoid structures in cancers: prognostic value, regulation, and manipulation for therapeutic intervention. . Front. Immunol. 7::407
     [Crossref] [Google Scholar]
  114. 114.
    Chen YE, Bousbaine D, Veinbachs A, Atabakhsh K, Dimas A, et al. 2023.. Engineered skin bacteria induce antitumor T cell responses against melanoma. . Science 380:(6641):203–10
     [Crossref] [Google Scholar]
  115. 115.
    Wang M, Rousseau B, Qiu K, Huang G, Zhang Y, et al. 2024.. Killing tumor-associated bacteria with a liposomal antibiotic generates neoantigens that induce anti-tumor immune responses. . Nat. Biotechnol. 42::126374
     [Crossref] [Google Scholar]
  116. 116.
    Kanehisa M, Goto S. 2000.. KEGG: Kyoto Encyclopedia of Genes and Genomes. . Nucleic Acids Res. 28:(1):27–30
     [Crossref] [Google Scholar]
  117. 117.
    Koh A, De Vadder F, Kovatcheva-Datchary P, Bäckhed F. 2016.. From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites. . Cell 165:(6):1332–45
     [Crossref] [Google Scholar]
  118. 118.
    Luu M, Riester Z, Baldrich A, Reichardt N, Yuille S, et al. 2021.. Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer. . Nat. Commun. 12:(1):4077
     [Crossref] [Google Scholar]
  119. 119.
    Thiele Orberg E, Meedt E, Hiergeist A, Xue J, Heinrich P, et al. 2024.. Bacteria and bacteriophage consortia are associated with protective intestinal metabolites in patients receiving stem cell transplantation. . Nat. Cancer 5:(1):187–208
     [Crossref] [Google Scholar]
  120. 120.
    Lindner S, Miltiadous O, Ramos RJF, Paredes J, Kousa AI, et al. 2024.. Altered microbial bile acid metabolism exacerbates T cell-driven inflammation during graft-versus-host disease. . Nat. Microbiol. 9:(3):614–30
     [Crossref] [Google Scholar]
  121. 121.
    Gao RY, Shearn CT, Orlicky DJ, Battista KD, Alexeev EE, et al. 2021.. Bile acids modulate colonic MAdCAM-1 expression in a murine model of combined cholestasis and colitis. . Mucosal Immunol. 14:(2):479–90
     [Crossref] [Google Scholar]
  122. 122.
    Wang F, Yu T, Huang G, Cai D, Liang X, et al. 2015.. Gut microbiota community and its assembly associated with age and diet in Chinese centenarians. . J. Microbiol. Biotechnol. 25:(8):1195–204
     [Crossref] [Google Scholar]
  123. 123.
    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:(6391):eaan5931
     [Crossref] [Google Scholar]
  124. 124.
    Girisa S, Henamayee S, Parama D, Rana V, Dutta U, Kunnumakkara AB. 2021.. Targeting Farnesoid X receptor (FXR) for developing novel therapeutics against cancer. . Mol. Biomed. 2:(1):21
     [Crossref] [Google Scholar]
  125. 125.
    Tian H, Gui Y, Wei Y, Shang B, Sun J, et al. 2021.. Z-guggulsterone induces PD-L1 upregulation partly mediated by FXR, Akt and Erk1/2 signaling pathways in non-small cell lung cancer. . Int. Immunopharmacol. 93::107395
     [Crossref] [Google Scholar]
  126. 126.
    Steed AL, Christophi GP, Kaiko GE, Sun L, Goodwin VM, et al. 2017.. The microbial metabolite desaminotyrosine protects from influenza through type I interferon. . Science 357:(6350):498–502
     [Crossref] [Google Scholar]
  127. 127.
    Joachim L, Göttert S, Sax A, Steiger K, Neuhaus K, et al. 2023.. The microbial metabolite desaminotyrosine enhances T-cell priming and cancer immunotherapy with immune checkpoint inhibitors. . eBioMedicine 97::104834
     [Crossref] [Google Scholar]
  128. 128.
    Thiele Orberg E, Göttert S, Hiergeist A, Meedt E, Kleigrewe K, et al. 2021.. Microbial-derived metabolites induce epithelial recovery via the sting pathway in mice and men and protect from graft-versus-host disease. . Blood 138:(Suppl. 1):87
     [Crossref] [Google Scholar]
  129. 129.
    Bhandari MP, Polaka I, Vangravs R, Mezmale L, Veliks V, et al. 2023.. Volatile markers for cancer in exhaled breath—could they be the signature of the gut microbiota?. Molecules 28:(8):3488
     [Crossref] [Google Scholar]
  130. 130.
    Hoffmann DE, Von Rosenvinge EC, Roghmann M-C, Palumbo FB, McDonald D, Ravel J. 2024.. The DTC microbiome testing industry needs more regulation. . Science 383:(6688):1176–79
     [Crossref] [Google Scholar]
  131. 131.
    Santiago A, Panda S, Mengels G, Martinez X, Azpiroz F, et al. 2014.. Processing faecal samples: a step forward for standards in microbial community analysis. . BMC Microbiol. 14:(1):112
     [Crossref] [Google Scholar]
  132. 132.
    CORDIS. 2013.. METABOLOMICSSTANDARD—Metabolomics: defining the standards for sample preparation of small molecules. Final Rep. Summary FP7 , CORDIS, Eur. Comm., Brussels:. https://cordis.europa.eu/project/id/217895/reporting
    [Google Scholar]
  133. 133.
    García-Cárdenas JM, Indacochea A, Pesantez-Coronel D, Terán-Navas M, Aleaga A, et al. 2024.. Toward equitable precision oncology: monitoring racial and ethnic inclusion in genomics and clinical trials. . J. Clin. Oncol. Precis Oncol. 8::e2300398
     [Crossref] [Google Scholar]
  134. 134.
    Lancet. 2024.. Cancer research equity: innovations for the many, not the few. . Lancet 403:(10425):409
     [Crossref] [Google Scholar]
  135. 135.
    Liu Z, De Vries B, Gerritsen J, Smidt H, Zoetendal EG. 2020.. Microbiome-based stratification to guide dietary interventions to improve human health. . Nutr. Res. 82::1–10
     [Crossref] [Google Scholar]
  136. 136.
    Lee KA, Thomas AM, Bolte LA, Björk JR, de Ruijter LK, et al. 2022.. Cross-cohort gut microbiome associations with immune checkpoint inhibitor response in advanced melanoma. . Nat. Med. 28:(3):535–44
     [Crossref] [Google Scholar]
  137. 137.
    Golčić M, Simetić L, Herceg D, Blažičević K, Kenđel Jovanović G, et al. 2023.. Analysis of the gut microbiome and dietary habits in metastatic melanoma patients with a complete and sustained response to immunotherapy. . Cancers 15:(11):3052
     [Crossref] [Google Scholar]
  138. 138.
    Dora D, Ligeti B, Kovacs T, Revisnyei P, Galffy G, et al. 2023.. Non-small cell lung cancer patients treated with Anti-PD1 immunotherapy show distinct microbial signatures and metabolic pathways according to progression-free survival and PD-L1 status. . OncoImmunology 12:(1):2204746
     [Crossref] [Google Scholar]
  139. 139.
    Chau J, Yadav M, Liu B, Furqan M, Dai Q, et al. 2021.. Prospective correlation between the patient microbiome with response to and development of immune-mediated adverse effects to immunotherapy in lung cancer. . BMC Cancer 21:(1):808
     [Crossref] [Google Scholar]
  140. 140.
    Xu L, Ma Y, Fang C, Peng Z, Gao F, et al. 2022.. Genomic and microbial factors affect the prognosis of anti-pd-1 immunotherapy in nasopharyngeal carcinoma. . Front. Oncol. 12::953884
     [Crossref] [Google Scholar]
  141. 141.
    Spiliopoulou P, Rooney A, Genta S, Kulikova M, Wang BX, et al. 2023.. Intestinal microbiome characterization in immune checkpoint inhibition (ICI) resistant disease. . J. Clin. Oncol. 41:(16_Suppl.):2515
     [Crossref] [Google Scholar]
/content/journals/10.1146/annurev-pharmtox-061124-102218
Loading
Gut Microbiota–Related Biomarkers in Immuno-Oncology
Annual Review of Pharmacology and Toxicology 65, 333 (2025); https://doi.org/10.1146/annurev-pharmtox-061124-102218
/content/journals/10.1146/annurev-pharmtox-061124-102218
/content/journals/10.1146/annurev-pharmtox-061124-102218
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error