| Autor: |
Eric Tartour, Alain Gey, Marc-Olivier Timsit, Arnaud Méjean, Stéphane Oudard, Michael Peyromaure, Nadine Benhamouda, Emeline Vinatier, Camélia Radulescu, Lucie Biard, Mathilde Sibony, Patrice Ravel, Marion Mandavit, Hélène Roussel, Cécile Badoual, Saïk Urien, Virginie Verkarre, Pierre Combe, Charles Dariane, Clémence Granier |
| Rok vydání: |
2023 |
| DOI: |
10.1158/0008-5472.c.6509514.v1 |
| Popis: |
Inhibitory receptors expressed by T cells mediate tolerance to tumor antigens, with coexpression of these receptors exacerbating this dysfunctional state. Using the VectraR automated multiparametric immunofluorescence technique, we quantified intratumoral CD8+ T cells coexpressing the inhibitory receptors PD-1 and Tim-3 from patients with renal cell carcinoma (RCC). A second validation cohort measured the same parameters by cytometry. The percentage of tumor-infiltrating CD8+ T cells coexpressing PD-1 and Tim-3 correlated with an aggressive phenotype and a larger tumor size at diagnosis. Coexpression of PD-1 and Tim-3 above the median conferred a higher risk of relapse and a poorer 36-month overall survival. Notably, other CD8+T-cell subsets did not exert a similar effect on overall survival. Moreover, only the PD-1+Tim-3+ subset of CD8+ T cells exhibited impaired function after stimulation. Our findings establish intratumoral Tim-3+PD1+CD8+ T cells as critical mediators of an aggressive phenotype in RCC. Use of the Vectra tool may be useful to identify similarly critical prognostic and predictive biomarkers in other tumor types and their response to immunotherapy. Cancer Res; 77(5); 1075–82. ©2016 AACR. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
|
