Synapse - The ectonucleotidase CD39 identifies tumor-reactive CD8(+) T cells predictive of immune checkpoint blockade efficacy in human lung cancer

The ectonucleotidase CD39 identifies tumor-reactive CD8(+) T cells predictive of immune checkpoint blockade efficacy in human lung cancer Journal Article

Authors:	Chow, A.; Uddin, F. Z.; Liu, M.; Dobrin, A.; Nabet, B. Y.; Mangarin, L.; Lavin, Y.; Rizvi, H.; Tischfield, S. E.; Quintanal-Villalonga, A.; Chan, J. M.; Shah, N.; Allaj, V.; Manoj, P.; Mattar, M.; Meneses, M.; Landau, R.; Ward, M.; Kulick, A.; Kwong, C.; Wierzbicki, M.; Yavner, J.; Egger, J.; Chavan, S. S.; Farillas, A.; Holland, A.; Sridhar, H.; Ciampricotti, M.; Hirschhorn, D.; Guan, X.; Richards, A. L.; Heller, G.; Mansilla-Soto, J.; Sadelain, M.; Klebanoff, C. A.; Hellmann, M. D.; Sen, T.; de Stanchina, E.; Wolchok, J. D.; Merghoub, T.; Rudin, C. M.
Article Title:	The ectonucleotidase CD39 identifies tumor-reactive CD8(+) T cells predictive of immune checkpoint blockade efficacy in human lung cancer
Abstract:	Improved identification of anti-tumor T cells is needed to advance cancer immunotherapies. CD39 expression is a promising surrogate of tumor-reactive CD8+ T cells. Here, we comprehensively profiled CD39 expression in human lung cancer. CD39 expression enriched for CD8+ T cells with features of exhaustion, tumor reactivity, and clonal expansion. Flow cytometry of 440 lung cancer biospecimens revealed weak association between CD39+ CD8+ T cells and tumoral features, such as programmed death-ligand 1 (PD-L1), tumor mutation burden, and driver mutations. Immune checkpoint blockade (ICB), but not cytotoxic chemotherapy, increased intratumoral CD39+ CD8+ T cells. Higher baseline frequency of CD39+ CD8+ T cells conferred improved clinical outcomes from ICB therapy. Furthermore, a gene signature of CD39+ CD8+ T cells predicted benefit from ICB, but not chemotherapy, in a phase III clinical trial of non-small cell lung cancer. These findings highlight CD39 as a proxy of tumor-reactive CD8+ T cells in human lung cancer. © 2022 Elsevier Inc.
Keywords:	genetics; cd8+ t lymphocyte; cd8-positive t-lymphocytes; carcinoma, non-small-cell lung; lung neoplasms; lung tumor; immunotherapy; drug therapy; non-small cell lung cancer; non small cell lung cancer; immune checkpoint blockade; cd8+ t cells; humans; human; immune checkpoint inhibitors; tumor mutation burden; t cell receptors
Journal Title:	Immunity
Volume:	56
Issue:	1
ISSN:	1074-7613
Publisher:	Cell Press
Date Published:	2023-01-10
Start Page:	93
End Page:	106.e6
Language:	English
DOI:	10.1016/j.immuni.2022.12.001
PUBMED:	36574773
PROVIDER:	scopus
PMCID:	PMC9887636
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85145981685&doi=10.1016%2fj.immuni.2022.12.001&partnerID=40&md5=cd125f6cde462da4a3d1fb46aa4f38a0
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF. Corresponding MSK authors are Andrew Chow and Charles M. Rudin. -- Export Date: 1 February 2023 -- Source: Scopus