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.
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
Title and authors | Publication | Year |
---|---|---|
Patterns of TIGIT Expression in Lymphatic Tissue, Inflammation, and Cancer
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Disease Markers | 2019 |
FcγR-Binding Is an Important Functional Attribute for Immune Checkpoint Antibodies in Cancer Immunotherapy
X Chen, X Song, K Li, T Zhang |
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CD96 Is an Immune Checkpoint That Regulates CD8 + T-cell Antitumor Function
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 |
T Cell Dysfunction in Cancer Immunity and Immunotherapy
A Xia, Y Zhang, J Xu, T Yin, XJ Lu |
Frontiers in immunology | 2019 |
Expression of the immune checkpoint receptor TIGIT in seminoma
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 |
Oncology Letters | 2019 |
Biomarkers for Immunotherapy of Cancer: Methods and Protocols
M Thurin, A Cesano, FM Marincola |
2019 | |
A TIGIT-based chimeric co-stimulatory switch receptor improves T-cell anti-tumor function
S Hoogi, V Eisenberg, S Mayer, A Shamul, T Barliya, CJ Cohen |
Journal for ImmunoTherapy of Cancer | 2019 |
Expression of TIGIT/CD155 and correlations with clinical pathological features in human hepatocellular carcinoma
X Duan, J Liu, J Cui, B Ma, Q Zhou, X Yang, Z Lu, Y Du, C Su |
Molecular medicine reports | 2019 |
Current Perspectives in Cancer Immunotherapy
T Christofi, S Baritaki, L Falzone, M Libra, A Zaravinos |
Cancers | 2019 |
Targeting the TIGIT-PVR immune checkpoint axis as novel therapeutic option in breast cancer
H Stamm, L Oliveira-Ferrer, EM Grossjohann, J Muschhammer, V Thaden, F Brauneck, R Kischel, V Müller, C Bokemeyer, W Fiedler, J Wellbrock |
OncoImmunology | 2019 |
Inhibitory receptors and ligands beyond PD-1, PD-L1 and CTLA-4: breakthroughs or backups
LP Andrews, H Yano, DA Vignali |
Nature Immunology | 2019 |
TIGIT as an emerging immune checkpoint
H Harjunpää, C Guillerey |
Clinical & Experimental Immunology | 2019 |
Brain immunology and immunotherapy in brain tumours
JH Sampson, MD Gunn, PE Fecci, DM Ashley |
Nature Reviews Cancer | 2019 |
Tumor-Targeted Chemoimmunotherapy with Immune-Checkpoint Blockade for Enhanced Anti-Melanoma Efficacy
M Li, Y Yang, C Xu, J Wei, Y Liu, X Cun, Q Yu, X Tang, S Yin, Z Zhang, Q He |
The AAPS Journal | 2019 |
A Comprehensive Analysis of Key Immune Checkpoint Receptors on Tumor-Infiltrating T Cells From Multiple Types of Cancer
, R Wang, P Fan, X Yao, L Qin, Y Peng, M Ma, N Asley, X Chang, Y Feng, Y Hu, Y Zhang, C Li, G Fanning, S Jones, C Verrill, D Maldonado-Perez, P Sopp, C Waugh, S Taylor, S Mcgowan, V Cerundolo, C Conlon, A McMichael, S Lu, X Wang, N Li, T Dong |
Frontiers in Oncology | 2019 |
Engineered triple inhibitory receptor resistance improves anti-tumor CAR-T cell performance via CD56
F Zou, L Lu, J Liu, B Xia, W Zhang, Q Hu, W Liu, Y Zhang, Y Lin, S Jing, M Huang, B Huang, B Liu, H Zhang |
Nature Communications | 2019 |
HCV-specific CD4+ T cells of patients with acute and chronic HCV infection display high expression of TIGIT and other co-inhibitory molecules
C Ackermann, M Smits, R Woost, JM Eberhard, S Peine, S Kummer, M Marget, T Kuntzen, WW Kwok, AW Lohse, T Jacobs, T Boettler, JS zur Wiesch |
Scientific Reports | 2019 |
Harnessing innate immunity in cancer therapy
O Demaria, S Cornen, M Daëron, Y Morel, R Medzhitov, E Vivier |
Nature | 2019 |
Novel Targets for the Treatment of Melanoma
L Ambrosi, S Khan, RD Carvajal, J Yang |
Current Oncology Reports | 2019 |
Dehydrocorydaline inhibits cell proliferation, migration and invasion via suppressing MEK1/2-ERK1/2 cascade in melanoma H Hu, Z Dong, X Wang, L Bai, Q Lei, J Yang, L Li, Q Li, L Liu, Y Zhang, Y Ji, L Guo, Y Liu, H Cui |
OncoTargets and therapy | 2019 |
Gene Expression Profiling Reveals Distinct Molecular Subtypes of Esophageal Squamous Cell Carcinoma in Asian Populations
F Wang, Z Yan, J Lv, J Xin, Y Dang, X Sun, Y An, Y Qi, Q Jiang, W Zhu, Y Li, A Li, X Guo |
Neoplasia (New York, N.Y.) | 2019 |
The Rise of NK Cell Checkpoints as Promising Therapeutic Targets in Cancer Immunotherapy
H Sun, C Sun |
Frontiers in immunology | 2019 |
Exhaustion and senescence: two crucial dysfunctional states of T cells in the tumor microenvironment
Y Zhao, Q Shao, G Peng |
Cellular and Molecular Immunology | 2019 |
Prognostic value of CD8 + PD-1+ immune infiltrates and PDCD1 gene expression in triple negative breast cancer
J Yeong, JC Lim, B Lee, H Li, CC Ong, AA Thike, WH Yeap, Y Yang, AY Lim, TK Tay, J Liu, SC Wong, J Chen, EH Lim, J Iqbal, R Dent, EW Newell, PH Tan |
Journal for ImmunoTherapy of Cancer | 2019 |
Localized Treatment with Oncolytic Adenovirus Delta-24-RGDOX Induces Systemic Immunity against Disseminated Subcutaneous and Intracranial Melanomas
H Jiang, DH Shin, TT Nguyen, J Fueyo, X Fan, V Henry, CC Carrillo, Y Yi, MM Alonso, TL Collier, Y Yuan, FF Lang, C Gomez-Manzano |
Clinical cancer research | 2019 |
The Discovery of Biomarkers in Cancer Immunotherapy
AP George, TM Kuzel, Y Zhang, B Zhang |
Computational and Structural Biotechnology Journal | 2019 |
Expression of immune checkpoint receptors Indoleamine 2,3‐dioxygenase and T cell Ig and ITIM domain in metastatic versus nonmetastatic choroidal melanoma
G Stålhammar, S Seregard, HE Grossniklaus |
Cancer Medicine | 2019 |
Clinical significance of CD8 + T cell immunoreceptor with Ig and ITIM domains + in locally advanced gastric cancer treated with SOX regimen after D2 gastrectomy
W Tang, X Pan, D Han, D Rong, M Zhang, L Yang, J Ying, H Guan, Z Chen, X Wang |
OncoImmunology | 2019 |
Potential Use of Gluconate in Cancer Therapy
ME Mycielska, MT Mohr, K Schmidt, K Drexler, P Rümmele, S Haferkamp, HJ Schlitt, A Gaumann, J Adamski, EK Geissler |
Frontiers in Oncology | 2019 |
The immune response‐related mutational signatures and driver genes in non‐small‐cell lung cancer
H Chen, W Chong, C Teng, Y Yao, X Wang, X Li |
Cancer Science | 2019 |
TIGIT and PD-1 Mark Intratumoral T Cells with Reduced Effector Function in B-cell Non-Hodgkin Lymphoma
SE Josefsson, K Beiske, YN Blaker, MS Førsund, H Holte, B Østenstad, E Kimby, H Köksal, S Wälchli, B Bai, EB Smeland, R Levy, A Kolstad, K Huse, JH Myklebust |
Cancer immunology research | 2019 |
Upregulation of PD‐1 follows tumour development in the AOM/DSS model of inflammation‐induced colorectal cancer in mice
M Yassin, Z Sadowska, D Djurhuus, B Nielsen, P Tougaard, J Olsen, AE Pedersen |
Immunology | 2019 |
Immunotherapies for the Treatment of Uveal Melanoma—History and Future
Schank, Hassel |
Cancers | 2019 |
Targeting interferon signaling and CTLA-4 enhance the therapeutic efficacy of anti-PD-1 immunotherapy in preclinical model of HPV+ oral cancer
S Dorta-Estremera, VL Hegde, RB Slay, R Sun, AV Yanamandra, C Nicholas, S Nookala, G Sierra, MA Curran, KJ Sastry |
Journal for ImmunoTherapy of Cancer | 2019 |
Monoclonal Antibodies in Dermatooncology—State of the Art and Future Perspectives
M Bobrowicz, R Zagozdzon, J Domagala, R Vasconcelos-Berg, E Guenova, M Winiarska |
Cancers | 2019 |
Perspectives in immunotherapy: meeting report from the “Immunotherapy Bridge 2018” (28–29 November, 2018, Naples, Italy)
PA Ascierto, C Bifulco, L Buonaguro, LA Emens, RL Ferris, BA Fox, GM Delgoffe, J Galon, C Gridelli, M Merlano, P Nathan, K Odunsi, H Okada, CM Paulos, S Pignata, KA Schalper, S Spranger, G Tortora, H Zarour, LH Butterfield, I Puzanov |
Journal for ImmunoTherapy of Cancer | 2019 |
Mechanism of resistance to immune checkpoint inhibitors
M Pandey, M Ernstoff |
2019 | |
PD-1+ TIGIT+ CD8+ T cells are associated with pathogenesis and progression of patients with hepatitis B virus-related hepatocellular carcinoma
Liu X, Li M, Wang X, Dang Z, Jiang Y, Wang X, Kong Y, Yang Z |
Cancer Immunology, Immunotherapy | 2019 |