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Cancer Res. 2017 Mar 1;77(5):1075-1082. doi: 10.1158/0008-5472.CAN-16-0274. Epub 2016 Nov 21.

Tim-3 Expression on Tumor-Infiltrating PD-1+CD8+ T Cells Correlates with Poor Clinical Outcome in Renal Cell Carcinoma.

Author information

1
INSERM U970, Université Paris Descartes, Sorbonne Paris-Cité, Paris, France.
2
Department of Urology, Hôpital Européen Georges Pompidou, Paris, France.
3
Service d'Oncologie Médicale, Hôpital Européen Georges Pompidou, Paris, France.
4
Department of Pathology, Hôpital Européen Georges Pompidou, Paris, France.
5
EA08: Evaluation des Thérapeutiques et Pharmacologie Périnatale et Pédiatrique, Unité de Recherche Clinique Paris Centre, Paris, France.
6
CIC 1419 INSERM Cochin-Necker, Paris, France.
7
CNRS UMR5048 Centre de Biochimie Structurale, INSERM U554, Université de Montpellier 1 et 2, Montpellier, France.
8
Department of Pathology, Hôpital Cochin, Paris, France.
9
Université Paris Diderot Paris 7, Paris, France.
10
Department of Pathology, Hôpital Foch, Suresnes, France.
11
Service d'Immunologie Biologique, AP-HP, Hôpital Européen Georges Pompidou, Paris, France.
12
Department of Urology, Hôpital Cochin, Paris, France.
13
INSERM U970, Université Paris Descartes, Sorbonne Paris-Cité, Paris, France. eric.tartour@aphp.fr.

Abstract

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.

PMID:
27872087
DOI:
10.1158/0008-5472.CAN-16-0274
[Indexed for MEDLINE]
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