Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact

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.
View: Text | PDF
Research Article Oncology Article has an altmetric score of 31

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

  • Text
  • PDF
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

×

Total citations by year

Year: 2025 2024 2023 2022 2021 2020 2019 2018 2017 2016 2015 2009 Total
Citations: 15 51 66 56 68 51 38 36 30 18 8 1 438
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2021 (68)

Title and authors Publication Year
Anti-TIGIT differentially affects sepsis survival in immunologically experienced vs. previously naïve hosts
Yini Sun, Jerome C Anyalebechi, He Sun, Tetsuya Yumoto, Ming Xue, Danya Liu, Zhe Liang, Craig M Coopersmith, Mandy L. Ford
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
JCI Insight 2021
Immunotherapy and Gene Therapy for Oncoviruses Infections: A Review
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
Frontiers in Oncology 2021
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
Frontiers in Oncology 2021
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

← Previous 1 2 3 Next →

Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Posted by 3 X users
Referenced in 64 patents
On 1 Facebook pages
Referenced in 1 Wikipedia pages
542 readers on Mendeley
See more details