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 ...
    • Pancreatic Cancer (Jul 2025)
    • 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)
    • 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: 16 51 66 56 68 51 38 36 30 18 8 1 439
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 2025 (16)

Title and authors Publication Year
Resistance mechanisms to immune checkpoint inhibitors: updated insights
Alsaafeen BH, Ali BR, Elkord E
Molecular Cancer 2025
Advances in Cell and Immune Therapies for Melanoma
Timis T, Buruiana S, Dima D, Nistor M, Muresan XM, Cenariu D, Tigu AB, Tomuleasa C
Biomedicines 2025
Neoadjuvant anti-PD-1 alone or in combination with anti-TIGIT or an oncolytic virus in resectable stage IIIB–D melanoma: a phase 1/2 trial
Dummer R, Robert C, Scolyer RA, Taube JM, Tetzlaff MT, Menzies AM, Hill A, Grob JJ, Portnoy DC, Lebbe C, Khattak MA, Cohen J, Bar-Sela G, Mehmi I, Shapira-Frommer R, Meyer N, Webber AL, Ren Y, Fukunaga-Kalabis M, Krepler C, Long GV
Nature Medicine 2025
CD155 promotes the progression of colorectal cancer by restraining CD8+ T cells via the PI3K/AKT/NF-κB pathway
Liang R, Liu L, Ding D, Li Y, Ren J, Wei B
Cancer Immunology, Immunotherapy : CII 2025
TIGIT inhibitor M6223 as monotherapy or in combination with bintrafusp alfa in patients with advanced solid tumors: a first-in-human, phase 1, dose-escalation trial
Naing A, McKean M, Tolcher A, Victor A, Hu P, Gao W, Nogueira Filho MA, Kitzing T, Gleicher S, Holland D, Richter E, Tadjalli-Mehr K, Siu LL
Journal for Immunotherapy of Cancer 2025
Adaptive immune responses against common viruses are sustained and functional in end-of-life patients
Olofsson A, Humbert M, Rekha RS, Frankling MH, Lund-Johansen F, Bergman P, Björkhem-Bergman L, Karlsson AC
iScience 2025
Multi-omics in immunotherapy research for HNSCC: present situation and future perspectives
Liu XH, Wang GR, Zhong NN, Wang WY, Liu B, Li Z, Bu LL
NPJ Precision Oncology 2025
Pan-cancer analysis of co-inhibitory molecules revealing their potential prognostic and clinical values in immunotherapy
Ren X, Guo A, Geng J, Chen Y, Wang X, Zhou L, Shi L
Frontiers in Immunology 2025
Model‐Informed Selection of the Recommended Phase 2 Dosage for Anti‐TIGIT Immunotherapy Leveraging co‐Expressed PD‐1 Inhibitor Target Engagement
Kareva I, Hu P, Pierre V, Kitzing T, Victor A, Richter E, Gao W, Venkatakrishnan K, Zutshi A
Clinical Pharmacology and Therapeutics 2025
The role of immune checkpoints PD-1 and CTLA-4 in cardiovascular complications leading to heart failure
Huang S, Kang Y, Liu T, Xiong Y, Yang Z, Zhang Q
Frontiers in Immunology 2025
Heterogeneity of γδ T-cell subsets and their clinical correlation in patients with AML
Jiang S, Zheng S, Yao C, Ning D, Zou S, Zhan J, Lan T, Yi T, Jin Z, Wu X
Frontiers in Immunology 2025
Computational screening for natural compounds as potential immune checkpoint inhibitors against TIGIT, a new avenue in cancer immunotherapy.
Chakraborty A, Kumar A
Molecular diversity 2025
TIGIT deficiency promotes autoreactive CD4(+) T-cell responses through a metabolic‒epigenetic mechanism in autoimmune myositis.
Lai Y, Wang S, Ren T, Shi J, Qian Y, Wang S, Zhou M, Watanabe R, Li M, Ruan X, Wang X, Zhuang L, Ke Z, Yang N, Huang Y, Zhang H
Nature communications 2025
Unravelling T cell exhaustion through co‐inhibitory receptors and its transformative role in cancer immunotherapy
Xiang S, Li S, Xu J
Clinical and Translational Medicine 2025
B and T lymphocyte attenuator (BTLA) and PD-1 pathway dual blockade promotes antitumor immune responses by reversing CD8+ T-cell exhaustion in non-small cell lung cancer
Zhang Y, Yang Y, Zeng Y, Qu Q, Shen D, Mu C, Lei W, Su M, Mao J, Gao L, Liu Z, Chen C, Huang JA
Frontiers in Immunology 2025
Tumour- and Non-Tumour-Associated Factors That Modulate Response to PD-1/PD-L1 Inhibitors in Non-Small Cell Lung Cancer
Khalil M, Tsao MS
Cancers 2025

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
545 readers on Mendeley
See more details