The DOI matches its Crossref record; 45 of the 45 references it cites were found in a registry or an index.
TIGIT and PD-1 impair tumor antigen–specific CD8+ T cells in melanoma patients
Open accessAbstract
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.
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Cites
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F.-A., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E.-M., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,845
Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay-Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,256
Nivolumab plus Ipilimumab in Advanced Melanoma
Wolchok, J. D., Kluger, H., Callahan, M. K., Postow, M. A., Rizvi, N. A., Lesokhin, A. M., Segal, N. H., Ariyan, C. E., Gordon, R.-A., Reed, K., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1302369 · Cited by 4,230
Self-citationWherry, E. J. (2011) · Nature Immunology · doi:10.1038/ni.2035 · Cited by 4,062 · cited 1×
“There is now ample evidence that tumor antigen–specific (TA-specific) CD8 + T cells become dysfunctional and exhausted upon chronic antigen exposure, losing their capacity to proliferate, produce cytokines, and lyse tumor cells (2, 3).”
Restoring function in exhausted CD8 T cells during chronic viral infection
Barber, D. L., Wherry, E. J., Masopust, D., Zhu, B., Allison, J. P., Sharpe, A. H., Freeman, G. J., & Ahmed, R. (2006) · Nature · doi:10.1038/nature04444 · Cited by 3,986
The interaction of TIGIT with PVR and PVRL2 inhibits human NK cell cytotoxicity
Stanietsky, N., Simic, H., Arapovic, J., Toporik, A., Levy, O., Novik, A., Levine, Z., Beiman, M., Dassa, L., Achdout, H., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903474106 · Cited by 3,524
Safety and Tumor Responses with Lambrolizumab (Anti–PD-1) in Melanoma
Hamid, O., Robert, C., Daud, A., Hodi, F. S., Hwu, W.-J., Kefford, R., Wolchok, J. D., Hersey, P., Joseph, R. W., Weber, J. S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1305133 · Cited by 3,392
Self-citationTopalian, S. L., Sznol, M., McDermott, D. F., Kluger, H. M., Carvajal, R. D., Sharfman, W. H., Brahmer, J. R., Lawrence, D. P., Atkins, M. B., Powderly, J. D., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2013.53.0105 · Cited by 2,222
Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity
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Cited by
A guide to cancer immunotherapy: from T cell basic science to clinical practice
Waldman, A. D., Fritz, J. M., & Lenardo, M. J. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-0306-5 · Cited by 4,154
Fundamental Mechanisms of Immune Checkpoint Blockade Therapy
Wei, S. C., Duffy, C. R., & Allison, J. P. (2018) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0367 · Cited by 3,088
Lag-3, Tim-3, and TIGIT: co-inhibitory receptors with specialized functions in immune regulation
Anderson, A. C., Joller, N., & Kuchroo, V. K. (2016) · Immunity · doi:10.1016/j.immuni.2016.05.001 · Cited by 2,096
Thommen, D. S., & Schumacher, T. N. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.012 · Cited by 1,299
Combination cancer immunotherapy and new immunomodulatory targets
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Metadata
- Authors
- Chauvin, J.-M., Pagliano, O., Fourcade, J., Sun, Z., Wang, H., Sander, C., Kirkwood, J. M., Chen, T.-H. T., Maurer, M., Korman, A. J., & Zarour, H. M.
- Venue
- Journal of Clinical Investigation
- Published
- 2015-04-13
- Volume
- 125
- Issue
- 5
- Pages
- 2046-2058
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W1987165863
- Cited by
- 784
- References
- 45
- FWCI
- 20.67
- Type
- journal article
- Language
- en
- Open access
- green
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- Chauvin, J.-M., Pagliano, O., Fourcade, J., Sun, Z., Wang, H., Sander, C., Kirkwood, J. M., Chen, T.-H. T., Maurer, M., Korman, A. J., & Zarour, H. M. (2015). TIGIT and PD-1 impair tumor antigen–specific CD8+ T cells in melanoma patients. Journal of Clinical Investigation. https://doi.org/10.1172/jci80445
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