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Citations to this article

TIGIT and PD-1 impair tumor antigen–specific CD8+ T cells in melanoma patients
Joe-Marc Chauvin, … , Alan J. Korman, Hassane M. Zarour
Joe-Marc Chauvin, … , Alan J. Korman, Hassane M. Zarour
Published April 13, 2015
Citation Information: J Clin Invest. 2015;125(5):2046-2058. https://doi.org/10.1172/JCI80445.
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Research Article Oncology Article has an altmetric score of 31

TIGIT and PD-1 impair tumor antigen–specific CD8+ T cells in melanoma patients

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Abstract

T cell Ig and ITIM domain (TIGIT) is an inhibitory receptor expressed by activated T cells, Tregs, and NK cells. Here, we determined that TIGIT is upregulated on tumor antigen–specific (TA-specific) CD8+ T cells and CD8+ tumor-infiltrating lymphocytes (TILs) from patients with melanoma, and these TIGIT-expressing CD8+ T cells often coexpress the inhibitory receptor PD-1. Moreover, CD8+ TILs from patients exhibited downregulation of the costimulatory molecule CD226, which competes with TIGIT for the same ligand, supporting a TIGIT/CD226 imbalance in metastatic melanoma. TIGIT marked early T cell activation and was further upregulated by T cells upon PD-1 blockade and in dysfunctional PD-1+TIM-3+ TA-specific CD8+ T cells. PD-1+TIGIT+, PD-1–TIGIT+, and PD-1+TIGIT– CD8+ TILs had similar functional capacities ex vivo, suggesting that TIGIT alone, or together with PD-1, is not indicative of T cell dysfunction. However, in the presence of TIGIT ligand–expressing cells, TIGIT and PD-1 blockade additively increased proliferation, cytokine production, and degranulation of both TA-specific CD8+ T cells and CD8+ TILs. Collectively, our results show that TIGIT and PD-1 regulate the expansion and function of TA-specific CD8+ T cells and CD8+ TILs in melanoma patients and suggest that dual TIGIT and PD-1 blockade should be further explored to elicit potent antitumor CD8+ T cell responses in patients with advanced melanoma.

Authors

Joe-Marc Chauvin, Ornella Pagliano, Julien Fourcade, Zhaojun Sun, Hong Wang, Cindy Sander, John M. Kirkwood, Tseng-hui Timothy Chen, Mark Maurer, Alan J. Korman, Hassane M. Zarour

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Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2009 Total
Citations: 15 50 66 56 68 51 38 36 30 18 8 1 437
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Citations to this article in year 2019 (38)

Title and authors Publication Year
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X Chen, X Song, K Li, T Zhang
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D Mittal, A Lepletier, J Madore, AR Aguilera, K Stannard, SJ Blake, VL Whitehall, C Liu, ML Bettington, K Takeda, GV Long, RA Scolyer, R Lan, N Siemers, A Korman, MW Teng, RJ Johnston, WC Dougall, MJ Smyth
Cancer immunology research 2019
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A Xia, Y Zhang, J Xu, T Yin, XJ Lu
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A Hinsch, N Blessin, R Simon, M Kluth, K Fischer, C HubeMagg, W Li, G MakrypidiFraune, B Wellge, T Mandelkow, N Debatin, D Hflmayer, M Lennartz, G Sauter, J Izbicki, S Minner, F Bscheck, R Uhlig, D Dum, T Krech, A Luebke, C Wittmer, F Jacobsen, E Burandt, S Steurer, W Wilczak
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S Hoogi, V Eisenberg, S Mayer, A Shamul, T Barliya, CJ Cohen
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O Demaria, S Cornen, M Daëron, Y Morel, R Medzhitov, E Vivier
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Current Oncology Reports 2019

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