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 |
---|---|---|
Anti-TIGIT differentially affects sepsis survival in immunologically experienced vs. previously naïve hosts
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JCI Insight | 2021 |
TIGIT modulates sepsis-induced immune dysregulation in mice with pre-existing malignancy
Wenxiao Zhang, Jerome C Anyalebechi, Kimberly M Ramonell, Ching-wen Chen, Jianfeng Xie, Zhe Liang, Deena B. Chihade, Shunsuke Otani, Craig M. Coopersmith, Mandy L. Ford |
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NA de Almeida, CR de Almeida Ribeiro, JV Raposo, VS de Paula |
Viruses | 2021 |
Risk of Pneumonitis Associated With Immune Checkpoint Inhibitors in Melanoma: A Systematic Review and Network Meta-Analysis
YM Sun, W Li, ZY Chen, Y Wang |
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Natural Killer Cells and Regulatory T Cells Cross Talk in Hepatocellular Carcinoma: Exploring Therapeutic Options for the Next Decade
AG Bozward, F Warricker, YH Oo, SI Khakoo |
Frontiers in immunology | 2021 |
Clinical Insights Into Novel Immune Checkpoint Inhibitors
JB Lee, SJ Ha, HR Kim |
Frontiers in pharmacology | 2021 |
Immune Checkpoints in Cancers: From Signaling to the Clinic
C Pisibon, A Ouertani, C Bertolotto, R Ballotti, Y Cheli |
Cancers | 2021 |
Poliovirus receptor (PVR)-like protein cosignaling network: new opportunities for cancer immunotherapy
B Wu, C Zhong, Q Lang, Z Liang, Y Zhang, X Zhao, Y Yu, H Zhang, F Xu, Y Tian |
Journal of Experimental & Clinical Cancer Research | 2021 |
TIGIT/CD226 Axis Regulates Anti-Tumor Immunity
J Yeo, M Ko, DH Lee, Y Park, H Jin |
Pharmaceuticals (Basel, Switzerland) | 2021 |
Fine-Tuning the Tumour Microenvironment: Current Perspectives on the Mechanisms of Tumour Immunosuppression
JD Armitage, HV Newnes, A McDonnell, A Bosco, J Waithman |
Cells | 2021 |
TIGIT, the Next Step Towards Successful Combination Immune Checkpoint Therapy in Cancer
Z Ge, MP Peppelenbosch, D Sprengers, J Kwekkeboom |
Frontiers in immunology | 2021 |
TIGIT and PD1 Co-blockade Restores ex vivo Functions of Human Tumor-Infiltrating CD8+ T Cells in Hepatocellular Carcinoma
Z Ge, G Zhou, LC Carrascosa, E Gausvik, PP Boor, L Noordam, M Doukas, WG Polak, T Terkivatan, Q Pan, RB Takkenberg, J Verheij, JI Erdmann, JN IJzermans, MP Peppelenbosch, J Kraan, J Kwekkeboom, D Sprengers |
CMGH Cellular and Molecular Gastroenterology and Hepatology | 2021 |
TIGIT and PD-1 Immune Checkpoint Pathways Are Associated With Patient Outcome and Anti-Tumor Immunity in Glioblastoma
I Raphael, R Kumar, LH McCarl, K Shoger, L Wang, P Sandlesh, CT Sneiderman, J Allen, S Zhai, ML Campagna, A Foster, TC Bruno, S Agnihotri, B Hu, BA Castro, FS Lieberman, A Broniscer, AA Diaz, NM Amankulor, D Rajasundaram, IF Pollack, G Kohanbash |
Frontiers in immunology | 2021 |
Analysis of the Characteristics of TIGIT-Expressing CD3−CD56+NK Cells in Controlling Different Stages of HIV-1 Infection
X Zhang, X Lu, AK Cheung, Q Zhang, Z Liu, Z Li, L Yuan, R Wang, Y Liu, B Tang, H Xia, H Wu, T Zhang, B Su |
Frontiers in immunology | 2021 |
Profiling the inhibitory receptors LAG-3, TIM-3, and TIGIT in renal cell carcinoma reveals malignancy
K Takamatsu, N Tanaka, K Hakozaki, R Takahashi, Y Teranishi, T Murakami, R Kufukihara, N Niwa, S Mikami, T Shinojima, T Sasaki, Y Sato, H Kume, S Ogawa, K Kakimi, T Kamatani, F Miya, T Tsunoda, E Aimono, H Nishihara, K Sawada, T Imamura, R Mizuno, M Oya |
Nature Communications | 2021 |
TIGIT regulates apoptosis of risky memory T cell subsets implicated in belatacept‐resistant rejection
H Sun, CR Hartigan, C Chen, Y Sun, M Tariq, JM Robertson, SM Krummey, AK Mehta, ML Ford |
American Journal of Transplantation | 2021 |
Two Complementarity Immunotherapeutics in Non-Small-Cell Lung Cancer Patients—Mechanism of Action and Future Concepts
K Wojas-Krawczyk, P Krawczyk, M Gil, M Strzemski |
Cancers | 2021 |
A combination of PD‑1/PD‑L1 inhibitors: The prospect of overcoming the weakness of tumor immunotherapy (Review)
X Kong, P Lu, C Liu, Y Guo, Y Yang, Y Peng, F Wang, Z Bo, X Dou, H Shi, J Meng |
Molecular medicine reports | 2021 |
Prognostic Role of TIGIT Expression in Patients with Solid Tumors: A Meta-Analysis
K Xiao, K Xiao, K Li, P Xue, S Zhu, MD Bagatini |
Journal of Immunology Research | 2021 |
An engineered oncolytic vaccinia virus encoding a single-chain variable fragment against TIGIT induces effective antitumor immunity and synergizes with PD-1 or LAG-3 blockade
S Zuo, M Wei, T Xu, L Kong, B He, S Wang, S Wang, J Wu, J Dong, J Wei |
Journal for ImmunoTherapy of Cancer | 2021 |
Potential of E3 Ubiquitin Ligases in Cancer Immunity: Opportunities and Challenges
P Ye, X Chi, JH Cha, S Luo, G Yang, X Yan, WH Yang |
Cells | 2021 |
Avelumab in Combination with Eribulin Mesylate in Metastatic Urothelial Carcinoma: BTCRC GU-051, a Phase 1b Study
M Joshi, S Holder, J Zhu, H Zheng, S Komanduri, J Warrick, H Yasin, R Garje, B Jia, J Drabick, D DeGraff, Y Zakharia |
European Urology Focus | 2021 |
Signal pathways of melanoma and targeted therapy
W Guo, H Wang, C Li |
Signal Transduction and Targeted Therapy | 2021 |
The CD112R/CD112 axis: a breakthrough in cancer immunotherapy
T Zeng, Y Cao, T Jin, Y Tian, C Dai, F Xu |
Journal of Experimental & Clinical Cancer Research | 2021 |
Targeting regulatory T cells for immunotherapy in melanoma
L Huang, Y Guo, S Liu, H Wang, J Zhu, L Ou, X Xu |
2021 | |
Nanobodies Enhancing Cancer Visualization, Diagnosis and Therapeutics
DB Naidoo, AA Chuturgoon |
International journal of molecular sciences | 2021 |
Examination of the TIGIT, CD226, CD112, and CD155 Immune Checkpoint Molecules in Peripheral Blood Mononuclear Cells in Women Diagnosed with Early-Onset Preeclampsia
L Szereday, DU Nagy, B Csiszar, D Kevey, T Feik, M Meggyes |
Biomedicines | 2021 |
Immune suppressive checkpoint interactions in the tumour microenvironment of primary liver cancers
G Zhou, PP Boor, MJ Bruno, D Sprengers, J Kwekkeboom |
British Journal of Cancer | 2021 |
The unfolded protein response links tumor aneuploidy to local immune dysregulation
S Xian, M Dosset, G Almanza, S Searles, P Sahani, TC Waller, K Jepsen, H Carter, M Zanetti |
EMBO reports | 2021 |
Immune Checkpoint Inhibitors in Human Glioma Microenvironment
A Ghouzlani, S Kandoussi, M Tall, KP Reddy, S Rafii, A Badou |
Frontiers in immunology | 2021 |
Immune Regulatory Processes of the Tumor Microenvironment under Malignant Conditions
K Pansy, B Uhl, J Krstic, M Szmyra, K Fechter, A Santiso, L Thüminger, H Greinix, J Kargl, K Prochazka, J Feichtinger, AJ Deutsch |
International journal of molecular sciences | 2021 |
Detection of Immune Checkpoint Receptors – A Current Challenge in Clinical Flow Cytometry
B Shibru, K Fey, S Fricke, AR Blaudszun, F Fürst, M Weise, S Seiffert, MK Weyh, U Köhl, U Sack, A Boldt |
Frontiers in immunology | 2021 |
Immune checkpoint inhibition for pancreatic ductal adenocarcinoma: limitations and prospects: a systematic review
HB Li, ZH Yang, QQ Guo |
Cell Communication and Signaling | 2021 |
Immune Checkpoints: Therapeutic Targets for Pituitary Tumors
D Nie, Y Xue, Q Fang, J Cheng, B Li, D Wang, C Li, S Gui, Y Zhang, P Zhao, X Zeng |
Disease Markers | 2021 |
Δ133p53α enhances metabolic and cellular fitness of TCR-engineered T cells and promotes superior antitumor immunity
KJ Legscha, EA Ferreira, A Chamoun, A Lang, MH Awwad, GN Ton, D Galetzka, B Guezguez, M Hundemer, JC Bourdon, M Munder, M Theobald, H Echchannaoui |
Journal for ImmunoTherapy of Cancer | 2021 |
Activated Lymphocytes and Increased Risk of Dermatologic Adverse Events during Sorafenib Therapy for Hepatocellular Carcinoma
J Corominas, V Sapena, M Sanduzzi-Zamparelli, C Millán, E Samper, N Llarch, G Iserte, F Torres, LG Fonseca, S Muñoz-Martínez, A Forner, J Bruix, L Boix, M Reig |
Cancers | 2021 |
Role of CD8+ T lymphocyte cells: Interplay with stromal cells in tumor microenvironment
Q Xie, J Ding, Y Chen |
Acta pharmaceutica Sinica. B | 2021 |
Clinical Efficacy and Future Prospects of Immunotherapy in Lung Cancer
T Kinoshita, H Terai, T Yaguchi |
Life Sciences | 2021 |
Adenosine Receptor Antagonists to Combat Cancer and to Boost Anti-Cancer Chemotherapy and Immunotherapy
R Franco, R Rivas-Santisteban, G Navarro, I Reyes-Resina |
Cells | 2021 |
Toward personalized treatment approaches for non-small-cell lung cancer
M Wang, RS Herbst, C Boshoff |
Nature Medicine | 2021 |
Immune Aging and Immunotherapy in Cancer
M Kaiser, MD Semeraro, M Herrmann, G Absenger, A Gerger, W Renner |
International journal of molecular sciences | 2021 |
Prognostic Role of Immune Checkpoint Regulators in Cholangiocarcinoma: A Pilot Study
L Cao, P Prithviraj, R Shrestha, R Sharma, M Anaka, KR Bridle, G Kannourakis, DH Crawford, A Jayachandran |
Journal of Clinical Medicine | 2021 |
Immune checkpoint CD155 promoter methylation profiling reveals cancer-associated behaviors within breast neoplasia
H Triki, K Declerck, S Charfi, WB Kridis, K Chaabane, SB Halima, T Sellami, A Rebai, WV Berghe, B Cherif |
Cancer Immunology, Immunotherapy | 2021 |
A reporter gene assay for determining the biological activity of therapeutic antibodies targeting TIGIT
Z Fu, H Liu, L Wang, C Yu, Y Yang, M Feng, J Wang |
Acta pharmaceutica Sinica. B | 2021 |
Classification of node-positive melanomas into prognostic subgroups using keratin, immune, and melanogenesis expression patterns
D Netanely, S Leibou, R Parikh, N Stern, H Vaknine, R Brenner, S Amar, RH Factor, T Perluk, J Frand, E Nizri, D Hershkovitz, V Zemser-Werner, C Levy, R Shamir |
Oncogene | 2021 |
Addition of anti-TIM3 or anti-TIGIT Antibodies to anti-PD1 Blockade Augments Human T cell Adoptive Cell Transfer
M Martinez, S Kim, NS Jean, S OBrien, L Lian, J Sun, RI Verona, E Moon |
OncoImmunology | 2021 |
Programmed Death Ligand-1 (PD-L1) Is an Independent Negative Prognosticator in Western-World Gallbladder Cancer
T Albrecht, F Brinkmann, M Albrecht, AS Lonsdorf, A Mehrabi, K Hoffmann, Y Kulu, A Charbel, MN Vogel, C Rupp, B Köhler, C Springfeld, P Schirmacher, S Roessler, B Goeppert |
Cancers | 2021 |
COM902, a novel therapeutic antibody targeting TIGIT augments anti-tumor T cell function in combination with PVRIG or PD-1 pathway blockade
K Hansen, S Kumar, K Logronio, S Whelan, S Qurashi, HY Cheng, A Drake, M Tang, P Wall, D Bernados, L Leung, E Ophir, Z Alteber, G Cojocaru, M Galperin, M Frenkel, M White, J Hunter, SC Liang, MF Kotturi |
Cancer Immunology, Immunotherapy | 2021 |
Phase I/II clinical trial of adoptive cell transfer of sorted specific T cells for metastatic melanoma patients
B Dréno, A Khammari, A Fortun, V Vignard, S Saiagh, T Beauvais, N Jouand, S Bercegay, S Simon, F Lang, N Labarrière |
Cancer Immunology, Immunotherapy | 2021 |
Clinical Perspectives to Overcome Acquired Resistance to Anti–Programmed Death-1 and Anti–Programmed Death Ligand-1 Therapy in Non-Small Cell Lung Cancer
YJ Lee, JB Lee, SJ Ha, HR Kim |
Molecules and Cells | 2021 |
Immunomodulation of T Helper Cells by Tumor Microenvironment in Oral Cancer Is Associated With CCR8 Expression and Rapid Membrane Vitamin D Signaling Pathway
M Fraga, M Yáñez, M Sherman, F Llerena, M Hernandez, G Nourdin, F Álvarez, J Urrizola, C Rivera, L Lamperti, L Nova, S Castro, O Zambrano, A Cifuentes, L Campos, S Moya, Juan, M Nuñez, J Gatica, J Figueroa, F Zúñiga, C Salomón, G Cerda, R Puentes, G Labarca, M Vidal, R McGregor, E Nova-Lamperti |
Frontiers in immunology | 2021 |
Development and Validation of a CD8+ T Cell Infiltration-Related Signature for Melanoma Patients
Y Yuan, Z Zhu, Y Lan, S Duan, Z Zhu, , G Li, H Qu, Y Feng, H Cai, Z Song |
Frontiers in immunology | 2021 |
A Randomized Placebo-Controlled Efficacy Study of a Prime Boost Therapeutic Vaccination Strategy in HIV-1-Infected Individuals: VRI02 ANRS 149 LIGHT Phase II Trial
Y Lévy, C Lacabaratz, E Lhomme, A Wiedemann, C Bauduin, C Fenwick, E Foucat, M Surenaud, L Guillaumat, V Boilet, V Rieux, O Bouchaud, PM Girard, JM Molina, P Morlat, L Hocqueloux, L Richert, G Pantaleo, JD Lelièvre, R Thiébaut, G Silvestri |
Journal of virology | 2021 |
The Tumor Microenvironment Factors That Promote Resistance to Immune Checkpoint Blockade Therapy
BL Russell, SA Sooklal, ST Malindisa, LJ Daka, M Ntwasa |
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Targeting the Tumor Microenvironment for Improving Therapeutic Effectiveness in Cancer Immunotherapy: Focusing on Immune Checkpoint Inhibitors and Combination Therapies
IT Chyuan, CL Chu, PN Hsu |
Cancers | 2021 |
Clinical Significance of Tumor Microenvironment in Acral Melanoma: A Large Single-Institution Study of Caucasians
AM Borkowska, A Szumera-Ciećkiewicz, M Chraszczewska, K Sokół, T Goryń, PŁ Rutkowski |
Journal of Clinical Medicine | 2021 |
TIGIT-related transcriptome profile and its association with tumor immune microenvironment in breast cancer
Q Zhang, C Gao, J Shao, Z Wang |
Bioscience Reports | 2021 |
Expression of Senescence Marker TIGIT Identifies Polyfunctional Donor-Reactive CD4+ T Cells Preferentially Lost After Kidney Transplantation
AC van der List, NH Litjens, M Klepper, MG Betjes |
Frontiers in immunology | 2021 |
sCD28, sCD80, sCTLA-4, and sBTLA Are Promising Markers in Diagnostic and Therapeutic Approaches for Aseptic Loosening and Periprosthetic Joint Infection
JM Jubel, TM Randau, J Becker-Gotot, S Scheidt, MD Wimmer, H Kohlhof, C Burger, DC Wirtz, FA Schildberg |
Frontiers in immunology | 2021 |
Bone Marrow-Resident Vδ1 T Cells Co-express TIGIT With PD-1, TIM-3 or CD39 in AML and Myeloma
F Brauneck, P Weimer, JS zur Wiesch, K Weisel, L Leypoldt, G Vohwinkel, B Fritzsche, C Bokemeyer, J Wellbrock, W Fiedler |
Frontiers in Medicine | 2021 |
A pan-cancer analysis revealing the role of TIGIT in tumor microenvironment
J Wen, X Mao, Q Cheng, Z Liu, F Liu |
Scientific Reports | 2021 |
Peptide vaccine targeting mutated GNAS : a potential novel treatment for pseudomyxoma peritonei
K Flatmark, A Torgunrud, KG Fleten, B Davidson, HV Juul, N Mensali, C Lund-Andersen, EM Inderberg |
Journal for ImmunoTherapy of Cancer | 2021 |
Increased frequency of TIGIT + CD73-CD8 + T cells with a TOX + TCF-1low profile in patients with newly diagnosed and relapsed AML
F Brauneck, F Haag, R Woost, N Wildner, E Tolosa, A Rissiek, G Vohwinkel, J Wellbrock, C Bokemeyer, JS zur Wiesch, C Ackermann, W Fiedler |
OncoImmunology | 2021 |
Combined Blockade of TIGIT and CD39 or A2AR Enhances NK-92 Cell-Mediated Cytotoxicity in AML
F Brauneck, E Seubert, J Wellbrock, JS zur Wiesch, Y Duan, T Magnus, C Bokemeyer, F Koch-Nolte, S Menzel, W Fiedler |
International journal of molecular sciences | 2021 |
Hitting the complexity of the TIGIT-CD96-CD112R-CD226 axis for next-generation cancer immunotherapy
Jin HS, Park Y |
BMB Reports | 2021 |
Update of early phase clinical trials in cancer immunotherapy
Lee DH |
BMB Reports | 2021 |
Perspectives on immune checkpoint ligands: expression, regulation, and clinical implications
Moon J, Oh YM, Ha SJ |
BMB Reports | 2021 |
CRISPRi-mediated knock-down of PRDM1/BLIMP1 programs central memory differentiation in ex vivo-expanded human T cells
Azadbakht M, Sayadmanesh A, Nazer N, Ahmadi A, Hemmati S, Mohammadzade H, Ebrahimi M, Baharvand H, Khalaj B, Aghamaali MR, Basiri M |
BioImpacts : BI | 2021 |