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Abstract

Progress in our understanding of how tumor cells co-opt immune checkpoint receptor (ICR) regulation of the immune response to suppress T cell function and how these proteins interact in the tumor microenvironment has resulted in the development of a plethora of therapeutic ICR monoclonal antibodies. While anti-CTLA-4 and anti-PD-1/PD-L1 therapies have provided meaningful clinical benefit in patients with certain cancers, many patients either do not respond or experience disease progression. As such, dual blockade of PD-1/PD-L1 and ICRs with alternative mechanisms of action has the potential to improve outcomes in patients with cancer. In this review, we focus on the biology of and clinical investigations into two promising ICR targets: LAG-3 and TIGIT. The data suggest that blockade of these ICRs in combination with PD-1/PD-L1 in immune-sensitive tumors could enhance anti-PD-1 efficacy without increased toxicity, facilitate combinations with standard-of-care therapies, and extend treatment benefit to more patients.

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2024-06-12
2024-10-06
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Literature Cited

  1. Anderson AC, Joller N, Kuchroo VK. 2016.. Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation. . Immunity 44::9891004
    [Crossref] [Google Scholar]
  2. Anderson AE, Lopez A, Udyavar A, Narasappa N, Lee S, et al. 2019.. Characterization of AB154, a humanized, non-depleting α-TIGIT antibody undergoing clinical evaluation in subjects with advanced solid tumors. Paper presented at Proceedings of the SITC Annual Meeting, National Harbor, MD:, Nov. 6–10
    [Google Scholar]
  3. Anderson NM, Simon MC. 2020.. The tumor microenvironment. . Curr. Biol. 30::R92125
    [Crossref] [Google Scholar]
  4. Andreae S, Piras F, Burdin N, Triebel F. 2002.. Maturation and activation of dendritic cells induced by lymphocyte activation gene-3 (CD223). . J. Immunol. 168::387480
    [Crossref] [Google Scholar]
  5. Andrews LP, Somasundaram A, Moskovitz JM, Szymczak-Workman AL, Liu C, et al. 2020.. Resistance to PD1 blockade in the absence of metalloprotease-mediated LAG3 shedding. . Sci. Immunol. 5::eabc2728
    [Crossref] [Google Scholar]
  6. Ascierto PA, Melero I, Bhatia S, Bono P, Sanborn RE, et al. 2017.. Initial efficacy of anti-lymphocyte activation gene-3 (anti–LAG-3; BMS-986016) in combination with nivolumab (nivo) in pts with melanoma (MEL) previously treated with anti–PD-1/PD-L1 therapy. . J. Clin. Oncol. 35::9520-20
    [Crossref] [Google Scholar]
  7. Baitsch L, Baumgaertner P, Devêvre E, Raghav SK, Legat A, et al. 2011.. Exhaustion of tumor-specific CD8+ T cells in metastases from melanoma patients. . J. Clin. Investig. 121::235060
    [Crossref] [Google Scholar]
  8. Banta KL, Xu X, Chitre AS, Au-Yeung A, Takahashi C, et al. 2022.. Mechanistic convergence of the TIGIT and PD-1 inhibitory pathways necessitates co-blockade to optimize anti-tumor CD8+ T cell responses. . Immunity 55::51226.e9
    [Crossref] [Google Scholar]
  9. Bauché D, Joyce-Shaikh B, Jain R, Grein J, Ku KS, et al. 2018.. LAG3+ regulatory T cells restrain interleukin-23-producing CX3CR1+ gut-resident macrophages during group 3 innate lymphoid cell-driven colitis. . Immunity 49::34252.e5
    [Crossref] [Google Scholar]
  10. Bendell JC, Bedard P, Bang Y-J, LoRusso P, Hodi S, et al. 2020.. Phase Ia/Ib dose-escalation study of the anti-TIGIT antibody tiragolumab as a single agent and in combination with atezolizumab in patients with advanced solid tumors. . Cancer Res. 80::CT302
    [Crossref] [Google Scholar]
  11. Bi J, Tian Z. 2019.. NK cell dysfunction and checkpoint immunotherapy. . Front. Immunol. 10::1999
    [Crossref] [Google Scholar]
  12. Chauvin J-M, Pagliano O, Fourcade J, Sun Z, Wang H, et al. 2015.. TIGIT and PD-1 impair tumor antigen–specific CD8+ T cells in melanoma patients. . J. Clin. Investig. 125::204658
    [Crossref] [Google Scholar]
  13. Chen X, Song X, Li K, Zhang T. 2019.. FcγR-binding is an important functional attribute for immune checkpoint antibodies in cancer immunotherapy. . Front. Immunol. 10::292
    [Crossref] [Google Scholar]
  14. Chen X, Xue L, Ding X, Zhang J, Jiang L, et al. 2022.. An Fc-competent anti-human TIGIT blocking antibody ociperlimab (BGB-A1217) elicits strong immune responses and potent anti-tumor efficacy in pre-clinical models. . Front. Immunol. 13::828319
    [Crossref] [Google Scholar]
  15. Cho BC, Abreu DR, Hussein M, Cobo M, Patel AJ, et al. 2022.. Tiragolumab plus atezolizumab versus placebo plus atezolizumab as a first-line treatment for PD-L1-selected non-small-cell lung cancer (CITYSCAPE): primary and follow-up analyses of a randomised, double-blind, phase 2 study. . Lancet Oncol. 23::78192
    [Crossref] [Google Scholar]
  16. Chung HC, Ros W, Delord J-P, Perets R, Italiano A, et al. 2019.. Efficacy and safety of pembrolizumab in previously treated advanced cervical cancer: results from the phase II KEYNOTE-158 study. . J. Clin. Oncol. 37::147078
    [Crossref] [Google Scholar]
  17. Cohen M, Giladi A, Barboy O, Hamon P, Li B, et al. 2022.. The interaction of CD4+ helper T cells with dendritic cells shapes the tumor microenvironment and immune checkpoint blockade response. . Nat. Cancer 3::30317
    [Crossref] [Google Scholar]
  18. Diaz LA Jr., Shiu K-K, Kim T-W, Jensen BV, Jensen LH, et al. 2022.. Pembrolizumab versus chemotherapy for microsatellite instability-high or mismatch repair-deficient metastatic colorectal cancer (KEYNOTE-177): final analysis of a randomised, open-label, phase 3 study. . Lancet Oncol. 23::65970
    [Crossref] [Google Scholar]
  19. Dixon KO, Schorer M, Nevin J, Etminan Y, Amoozgar Z, et al. 2018.. Functional anti-TIGIT antibodies regulate development of autoimmunity and antitumor immunity. . J. Immunol. 200::30007
    [Crossref] [Google Scholar]
  20. Dummer R, Robert C, Scolyer RA, Taube JM, Tetzlaff MT, et al. 2023.. KEYMAKER-U02 substudy 02C: neoadjuvant pembrolizumab (pembro) + vibostolimab (vibo) or gebasaxturev (geba) or pembro alone followed by adjuvant pembro for stage IIIB-D melanoma. . Cancer Res. 83::CT002
    [Crossref] [Google Scholar]
  21. El Halabi L, Adam J, Gravelle P, Marty V, Danu A, et al. 2021.. Expression of the immune checkpoint regulators LAG-3 and TIM-3 in classical Hodgkin lymphoma. . Clin. Lymphoma Myeloma Leuk. 21::25766.e3
    [Crossref] [Google Scholar]
  22. Garassino MC, Gadgeel S, Speranza G, Felip E, Esteban E, et al. 2023.. Pembrolizumab plus pemetrexed and platinum in nonsquamous non–small-cell lung cancer: 5-year outcomes from the phase 3 KEYNOTE-189 study. . J. Clin. Oncol. 41::199298
    [Crossref] [Google Scholar]
  23. Garralda E, Sukari A, Lakhani NJ, Patnaik A, Lou Y, et al. 2021.. A phase 1 first-in-human study of the anti-LAG-3 antibody MK4280 (favezelimab) plus pembrolizumab in previously treated, advanced microsatellite stable colorectal cancer. . J. Clin. Oncol. 39::3584
    [Crossref] [Google Scholar]
  24. Garralda E, Sukari A, Lakhani NJ, Patnaik A, Lou Y, et al. 2022.. A first-in-human study of the anti-LAG-3 antibody favezelimab plus pembrolizumab in previously treated, advanced microsatellite stable colorectal cancer. . ESMO Open 7::100639
    [Crossref] [Google Scholar]
  25. Giunta EF, Addeo A, Rizzo A, Banna GL. 2022.. First-line treatment for advanced SCLC: What is left behind and beyond chemoimmunotherapy. . Front. Med. 9::924853
    [Crossref] [Google Scholar]
  26. Guy C, Mitrea DM, Chou P-C, Temirov J, Vignali KM, et al. 2022.. LAG3 associates with TCR–CD3 complexes and suppresses signaling by driving co-receptor–Lck dissociation. . Nat. Immunol. 23::75767
    [Crossref] [Google Scholar]
  27. Hamid O, Weise A, Kim TM, McKean MA, Lakhani NJ, et al. 2022.. 790MO Phase I study of fianlimab, a human lymphocyte activation gene-3 (LAG-3) monoclonal antibody, in combination with cemiplimab in advanced melanoma (mel). . Ann. Oncol. 33::S905
    [Crossref] [Google Scholar]
  28. Han J-H, Cai M, Grein J, Perera S, Wang H, et al. 2020.. Effective anti-tumor response by TIGIT blockade associated with FcγR engagement and myeloid cell activation. . Front. Immunol. 11::573405
    [Crossref] [Google Scholar]
  29. Han Q, Shi H, Liu F. 2016.. CD163+ M2-type tumor-associated macrophage support the suppression of tumor-infiltrating T cells in osteosarcoma. . Int. Immunopharmacol. 34::1016
    [Crossref] [Google Scholar]
  30. Hansen K, Kumar S, Logronio K, Whelan S, Qurashi S, et al. 2021.. COM902, a novel therapeutic antibody targeting TIGIT augments anti-tumor T cell function in combination with PVRIG or PD-1 pathway blockade. . Cancer Immunol. Immunother. 70::352540
    [Crossref] [Google Scholar]
  31. Herbst RS, Garon EB, Kim D-W, Cho BC, Gervais R, et al. 2021.. Five year survival update from KEYNOTE-010: pembrolizumab versus docetaxel for previously treated, programmed death-ligand 1-positive advanced NSCLC. . J. Thorac. Oncol. 16::171832
    [Crossref] [Google Scholar]
  32. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, et al. 2010.. Improved survival with ipilimumab in patients with metastatic melanoma. . New Engl. J. Med. 363::71123
    [Crossref] [Google Scholar]
  33. Huang C-T, Workman CJ, Flies D, Pan X, Marson AL, et al. 2004.. Role of LAG-3 in regulatory T cells. . Immunity 21::50313
    [Crossref] [Google Scholar]
  34. Huard B, Mastrangeli R, Prigent P, Bruniquel D, Donini S, et al. 1997.. Characterization of the major histocompatibility complex class II binding site on LAG-3 protein. . PNAS 94::574449
    [Crossref] [Google Scholar]
  35. Huard B, Tournier M, Hercend T, Triebel F, Faure F. 1994.. Lymphocyte-activation gene 3/major histocompatibility complex class II interaction modulates the antigenic response of CD4+ T lymphocytes. . Eur. J. Immunol. 24::321621
    [Crossref] [Google Scholar]
  36. Isaacs C, Nanda R, Chien J, Trivedi MS, Stringer-Reasor E, et al. 2022.. Evaluation of anti-PD-1 cemiplimab plus anti-LAG-3 REGN3767 in early-stage, high-risk HER2-negative breast cancer: Results from the neoadjuvant I-SPY 2 TRIAL. Paper presented at the 2022 San Antonio Breast Cancer Symposium, San Antonio, TX:, Dec. 8–11
    [Google Scholar]
  37. Jackson Z, Hong C, Schauner R, Dropulic B, Caimi PF, et al. 2022.. Sequential single-cell transcriptional and protein marker profiling reveals TIGIT as a marker of CD19 CAR-T cell dysfunction in patients with non-Hodgkin lymphoma. . Cancer Discov. 12::1886903
    [Crossref] [Google Scholar]
  38. Johnson ML, Fox W, Lee Y-G, Lee KH, Ahn HK, et al. 2022.. ARC-7: Randomized phase 2 study of domvanalimab + zimberelimab ± etrumadenant versus zimberelimab in first-line, metastatic, PD-L1-high non-small cell lung cancer (NSCLC). . J. Clin. Oncol. 40::397600
    [Crossref] [Google Scholar]
  39. Johnston RJ, Comps-Agrar L, Hackney J, Yu X, Huseni M, et al. 2014.. The immunoreceptor TIGIT regulates antitumor and antiviral CD8+ T cell effector function. . Cancer Cell 26::92337
    [Crossref] [Google Scholar]
  40. Kato K, Cho BC, Takahashi M, Okada M, Lin C-Y, et al. 2019.. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial. . Lancet Oncol. 20::150617
    [Crossref] [Google Scholar]
  41. Kouo T, Huang L, Pucsek AB, Cao M, Solt S, et al. 2015.. Galectin-3 shapes antitumor immune responses by suppressing CD8+ T cells via LAG-3 and inhibiting expansion of plasmacytoid dendritic cells. . Cancer Immunol. Res. 3::41223
    [Crossref] [Google Scholar]
  42. Kraehenbuehl L, Weng CH, Eghbali S, Wolchok JD, Merghoub T. 2022.. Enhancing immunotherapy in cancer by targeting emerging immunomodulatory pathways. . Nat. Rev. Clin. Oncol. 19::3750
    [Crossref] [Google Scholar]
  43. Kumar R, Kim SH, Zhong D, Lu S, Cheng Y, et al. 2022.. EP08.01-073 AdvanTIG-105: phase 1b dose-expansion study of ociperlimab plus tislelizumab in patients with metastatic NSCLC. . J. Thorac. Oncol. 17:: S37576
    [Crossref] [Google Scholar]
  44. Kurtulus S, Sakuishi K, Ngiow S-F, Joller N, Tan DJ, et al. 2015.. TIGIT predominantly regulates the immune response via regulatory T cells. . J. Clin. Investig. 125::405362
    [Crossref] [Google Scholar]
  45. Kuzevanova A, Apanovich N, Mansorunov D, Korotaeva A, Karpukhin A. 2022.. The features of checkpoint receptor-ligand interaction in cancer and the therapeutic effectiveness of their inhibition. . Biomedicines 10::2081
    [Crossref] [Google Scholar]
  46. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, et al. 2015.. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. . New Engl. J. Med. 373::2334
    [Crossref] [Google Scholar]
  47. Lauder SN, Smart K, Kersemans V, Allen D, Scott J, et al. 2020.. Enhanced antitumor immunity through sequential targeting of PI3Kδ and LAG3. . J. Immunother. Cancer 8::e000693
    [Crossref] [Google Scholar]
  48. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, et al. 2015.. PD-1 blockade in tumors with mismatch-repair deficiency. . New Engl. J. Med. 372::250920
    [Crossref] [Google Scholar]
  49. Lecocq Q, Keyaerts M, Devoogdt N, Breckpot K. 2020.. The next-generation immune checkpoint LAG-3 and its therapeutic potential in oncology: Third time's a charm. . Int. J. Mol. Sci. 22::75
    [Crossref] [Google Scholar]
  50. Lee JB, Ha SJ, Kim HR. 2021.. Clinical insights into novel immune checkpoint inhibitors. . Front. Pharmacol. 12::681320
    [Crossref] [Google Scholar]
  51. Li S, Li L, Pan T, Li X, Tong Y, Jin Y. 2022.. Prognostic value of TIGIT in East Asian patients with solid cancers: a systematic review, meta-analysis and pancancer analysis. . Front. Immunol. 13::977016
    [Crossref] [Google Scholar]
  52. Li Y, He M, Zhou Y, Yang C, Wei S, et al. 2019.. The prognostic and clinicopathological roles of PD-L1 expression in colorectal cancer: a systematic review and meta-analysis. . Front. Pharmacol. 10::139
    [Crossref] [Google Scholar]
  53. Liang B, Workman C, Lee J, Chew C, Dale BM, et al. 2008.. Regulatory T cells inhibit dendritic cells by lymphocyte activation gene-3 engagement of MHC class II. . J. Immunol. 180::591626
    [Crossref] [Google Scholar]
  54. Maio M, Ascierto PA, Manzyuk L, Motola-Kuba D, Penel N, et al. 2022.. Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study. . Ann. Oncol. 33::92938
    [Crossref] [Google Scholar]
  55. Mao X, Ou MT, Karuppagounder SS, Kam T-I, Yin X, et al. 2016.. Pathological α-synuclein transmission initiated by binding lymphocyte-activation gene 3. . Science 353::aah3374
    [Crossref] [Google Scholar]
  56. Marabelle A, Fakih M, Lopez J, Shah M, Shapira-Frommer R, et al. 2020.. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. . Lancet Oncol. 21::135365
    [Crossref] [Google Scholar]
  57. Martins GA, Cimmino L, Shapiro-Shelef M, Szabolcs M, Herron A, et al. 2006.. Transcriptional repressor Blimp-1 regulates T cell homeostasis and function. . Nat. Immunol. 7::45765
    [Crossref] [Google Scholar]
  58. Matulonis UA, Shapira-Frommer R, Santin AD, Lisyanskaya AS, Pignata S, et al. 2019.. Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study. . Ann. Oncol. 30::108087
    [Crossref] [Google Scholar]
  59. Mayer RJ, Van Cutsem E, Falcone A, Yoshino T, Garcia-Carbonero R, et al. 2015.. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. . New Engl. J. Med. 372::190919
    [Crossref] [Google Scholar]
  60. Mettu NB, Ulahannan SV, Bendell JC, Garrido-Laguna I, Strickler JH, et al. 2022.. A phase 1a/b open-label, dose-escalation study of etigilimab alone or in combination with nivolumab in patients with locally advanced or metastatic solid tumors. . Clin. Cancer Res. 28::88292
    [Crossref] [Google Scholar]
  61. Mu S, Liang Z, Wang Y, Chu W, Chen Y-L, et al. 2022.. PD-L1/TIGIT bispecific antibody showed survival advantage in animal model. . Clin. Transl. Med. 12::e754
    [Crossref] [Google Scholar]
  62. Murakami D, Matsuda K, Iwamoto H, Mitani Y, Mizumoto Y, et al. 2022.. Prognostic value of CD155/TIGIT expression in patients with colorectal cancer. . PLOS ONE 17::e0265908
    [Crossref] [Google Scholar]
  63. Najem H, Ott M, Kassab C, Rao A, Rao G, et al. 2022.. Central nervous system immune interactome is a function of cancer lineage, tumor microenvironment, and STAT3 expression. . JCI Insight 7::e157612
    [Crossref] [Google Scholar]
  64. Natoli M, Hatje K, Gulati P, Junker F, Herzig P, et al. 2022.. Deciphering molecular and cellular ex vivo responses to bispecific antibodies PD1-TIM3 and PD1-LAG3 in human tumors. . J. Immunother. Cancer 10::e005548
    [Crossref] [Google Scholar]
  65. Niu J, Maurice-Dror C, Lee DH, Kim DW, Nagrial A, et al. 2022.. First-in-human phase 1 study of the anti-TIGIT antibody vibostolimab as monotherapy or with pembrolizumab for advanced solid tumors, including non-small-cell lung cancer. . Ann. Oncol. 33::16980
    [Crossref] [Google Scholar]
  66. Novello S, Kowalski DM, Luft A, Gümüş M, Vicente D, et al. 2023.. Pembrolizumab plus chemotherapy in squamous non–small-cell lung cancer: 5-year update of the phase III KEYNOTE-407 study. . J. Clin. Oncol. 41::19992006
    [Crossref] [Google Scholar]
  67. O'Neil BH, Wallmark JM, Lorente D, Elez E, Raimbourg J, et al. 2017.. Safety and antitumor activity of the anti–PD-1 antibody pembrolizumab in patients with advanced colorectal carcinoma. . PLOS ONE 12::e0189848
    [Crossref] [Google Scholar]
  68. Patel SP, Othus M, Chen Y, Wright GP, Yost KJ, et al. 2023.. Neoadjuvant–adjuvant or adjuvant-only pembrolizumab in advanced melanoma. . New Engl. J. Med. 388::81323
    [Crossref] [Google Scholar]
  69. Perets R, Gutierrez M, Rha SY, Taylor S, Stein B, et al. 2022.. Abstract CT180: Safety and efficacy of vibostolimab (vibo) plus pembrolizumab (pembro) and coformulation of vibo/pembro in ovarian cancer naive to PD-1/PD-L1 inhibitors. . Cancer Res. 82::CT180
    [Crossref] [Google Scholar]
  70. Robert C, Thomas L, Bondarenko I, O'Day S, Weber J, et al. 2011.. Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. . N Engl. J. Med. 364::251726
    [Crossref] [Google Scholar]
  71. Rudin CM, Liu SV, Lu S, Soo RA, Hong MH, et al. 2022.. SKYSCRAPER-02: primary results of a phase III, randomized, double-blind, placebo-controlled study of atezolizumab (atezo) + carboplatin + etoposide (CE) with or without tiragolumab (tira) in patients (pts) with untreated extensive-stage small cell lung cancer (ES-SCLC). . J. Clin. Oncol. 40::LBA8507
    [Crossref] [Google Scholar]
  72. Sauer N, Szlasa W, Jonderko L, Oślizło M, Kunachowicz D, et al. 2022.. LAG-3 as a potent target for novel anticancer therapies of a wide range of tumors. . Int. J. Mol. Sci. 23::9958
    [Crossref] [Google Scholar]
  73. Shao D, Chen Y, Huang H, Liu Y, Chen J, et al. 2022.. LAG3 blockade coordinates with microwave ablation to promote CD8+ T cell-mediated anti-tumor immunity. . J. Transl. Med. 20::433
    [Crossref] [Google Scholar]
  74. Shapira-Frommer R, Perets R, Voskoboynik M, Mileham K, Nagrial A, et al. 2022.. Abstract CT508: Safety and efficacy of vibostolimab (vibo) plus pembrolizumab (pembro) in patients (pts) with cervical cancer naive to PD-1/PD-L1 inhibitors. . Cancer Res. 82::CT508
    [Crossref] [Google Scholar]
  75. Shi A-P, Tang X-Y, Xiong Y-L, Zheng K-F, Liu Y-J, et al. 2022.. Immune checkpoint LAG3 and its ligand FGL1 in cancer. . Front. Immunol. 12::785091
    [Crossref] [Google Scholar]
  76. Shigeoka M, Koma Y-I, Nishio M, Komori T, Yokozaki H. 2019.. CD163+ macrophages infiltration correlates with the immunosuppressive cytokine interleukin 10 expression in tongue leukoplakia. . Clin. Exp. Dental Res. 5::62737
    [Crossref] [Google Scholar]
  77. Shitara K, Golan T, Mileham K, Voskoboynik M, Rha S, et al. 2022.. PD-3 phase 1 trial of vibostolimab plus pembrolizumab for PD-1/PD-L1 inhibitor-naive advanced gastric cancer: the KEYVIBE-001 trial. . Ann. Oncol. 33::S240
    [Crossref] [Google Scholar]
  78. Shitara K, Özgüroğlu M, Bang Y-J, Di Bartolomeo M, Mandalà M, et al. 2018.. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. . Lancet 392::12333
    [Crossref] [Google Scholar]
  79. Sung E, Ko M, Won J-y, Jo Y, Park E, et al. 2022.. LAG-3xPD-L1 bispecific antibody potentiates antitumor responses of T cells through dendritic cell activation. . Mol. Ther. 30::280016
    [Crossref] [Google Scholar]
  80. Tawbi HA, Schadendorf D, Lipson EJ, Ascierto PA, Matamala L, et al. 2022.. Relatlimab and nivolumab versus nivolumab in untreated advanced melanoma. New Engl. . J. Med. 386::2434
    [Google Scholar]
  81. Tian X, Ning Q, Yu J, Tang S. 2022.. T-cell immunoglobulin and ITIM domain in cancer immunotherapy: a focus on tumor-infiltrating regulatory T cells. . Mol. Immunol. 147::6270
    [Crossref] [Google Scholar]
  82. Timmerman J, Lavie D, Johnson NA, Avigdor A, Borchmann P, et al. 2022.. Updated results from an open-label phase 1/2 study of favezelimab (anti-LAG-3) plus pembrolizumab in relapsed or refractory classical Hodgkin lymphoma after anti-PD-1 treatment. . Blood 140::76870
    [Crossref] [Google Scholar]
  83. Triebel F, Jitsukawa S, Baixeras E, Roman-Roman S, Genevee C, et al. 1990.. LAG-3, a novel lymphocyte activation gene closely related to CD4. . J. Exp. Med. 171::1393405
    [Crossref] [Google Scholar]
  84. Twomey JD, Zhang B. 2021.. Cancer immunotherapy update: FDA-approved checkpoint inhibitors and companion diagnostics. . AAPS J. 23::39
    [Crossref] [Google Scholar]
  85. Waight JD, Chand D, Dietrich S, Gombos R, Horn T, et al. 2018.. Selective FcγR co-engagement on APCs modulates the activity of therapeutic antibodies targeting T cell antigens. . Cancer Cell 33::103347.e5
    [Crossref] [Google Scholar]
  86. Wainberg Z, Matos I, Delord J, Cassier P, Gil-Martin M, et al. 2021.. LBA-5 phase Ib study of the anti-TIGIT antibody tiragolumab in combination with atezolizumab in patients with metastatic esophageal cancer. . Ann. Oncol. 32::S22728
    [Crossref] [Google Scholar]
  87. Wang J, Sanmamed MF, Datar I, Su TT, Ji L, et al. 2019.. Fibrinogen-like protein 1 is a major immune inhibitory ligand of LAG-3. . Cell 176::33447.e12
    [Crossref] [Google Scholar]
  88. Wang X, Teng F, Kong L, Yu J. 2016.. PD-L1 expression in human cancers and its association with clinical outcomes. . OncoTargets Ther. 9::502339
    [Crossref] [Google Scholar]
  89. Workman CJ, Cauley LS, Kim I-J, Blackman MA, Woodland DL, Vignali DAA. 2004.. Lymphocyte activation gene-3 (CD223) regulates the size of the expanding T cell population following antigen activation in vivo. . J. Immunol. 172::545055
    [Crossref] [Google Scholar]
  90. Workman CJ, Dugger KJ, Vignali DAA. 2002.. Cutting edge: molecular analysis of the negative regulatory function of lymphocyte activation gene-3. . J. Immunol. 169::539295
    [Crossref] [Google Scholar]
  91. Workman CJ, Vignali DAA. 2003.. The CD4-related molecule, LAG-3 (CD223), regulates the expansion of activated T cells. . Eur. J. Immunol. 33::97079
    [Crossref] [Google Scholar]
  92. Xiao K, Xiao K, Li K, Xue P, Zhu S. 2021.. Prognostic role of TIGIT expression in patients with solid tumors: a meta-analysis. . J. Immunol. Res. 2021::5440572
    [Google Scholar]
  93. Xu D, Zhao E, Zhu C, Zhao W, Wang C, et al. 2020.. TIGIT and PD-1 may serve as potential prognostic biomarkers for gastric cancer. . Immunobiology 225::151915
    [Crossref] [Google Scholar]
  94. Xu F, Liu J, Liu D, Liu B, Wang M, et al. 2014.. LSECtin expressed on melanoma cells promotes tumor progression by inhibiting antitumor T-cell responses. . Cancer Res. 74::341828
    [Crossref] [Google Scholar]
  95. Yang F, Zhao L, Wei Z, Yang Y, Liu J, et al. 2020.. A cross-species reactive TIGIT-blocking antibody Fc dependently confers potent antitumor effects. . J. Immunol. 205::215668
    [Crossref] [Google Scholar]
  96. Yu X, Harden K, Gonzalez LC, Francesco M, Chiang E, et al. 2009.. The surface protein TIGIT suppresses T cell activation by promoting the generation of mature immunoregulatory dendritic cells. . Nat. Immunol. 10::4857
    [Crossref] [Google Scholar]
  97. Yu Y, Huang D, Gao B, Zhao J, Hu Y, et al. 2022.. 1017P AdvanTIG-105: phase Ib dose-expansion study of ociperlimab (OCI) + tislelizumab (TIS) with chemotherapy (chemo) in patients (pts) with metastatic squamous (sq) and non-squamous (non-sq) non-small cell lung cancer (NSCLC). . Ann. Oncol. 33::S1019
    [Crossref] [Google Scholar]
  98. 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::72332
    [Crossref] [Google Scholar]
  99. Zhong Z, Zhang M, Ning Y, Mao G, Li X, et al. 2022.. Development of a bispecific antibody targeting PD-L1 and TIGIT with optimal cytotoxicity. . Sci. Rep. 12::18011
    [Crossref] [Google Scholar]
  100. Zinn S, Vazquez-Lombardi R, Zimmermann C, Sapra P, Jermutus L, Christ D. 2023.. Advances in antibody-based therapy in oncology. . Nat. Cancer 4::16580
    [Crossref] [Google Scholar]
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  • Article Type: Review Article
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