CD39 Identifies the CD4(+) Tumor-Specific T-cell Population in Human Cancer

Author(s):
Kortekaas, K.E.; Santegoets, S.J.; Sturm, G.; Ehsan, I.; Egmond, S.L. van; Finotello, F.; Trajanoski, Z.; Welters, M.J.P.; Poelgeest, M.I.E. van; Burg, S.H. van der (0000-0002-6556-0354)
Published
2020
Publication type
Article / Letter to editor

Abstract

The accumulation of tumor-specific CD4(+) and CD8(+) effector T cells is key to an effective antitumor response. Locally, CD4(+) T cells promote the recruitment and effector function of tumor-specific CD8(+) T cells and activate innate killer cells in the tumor. Here, we show that tumor-specific CD4(+) T cells were predominantly present in the CD39(+) subset of tumorinfiltrating lymphocytes (TIL). The CD39(+) CD4(+) and CD8(+) TILs were detected in three different tumor types, and displayed an activated (PD-1(+), HLA(-) DR+) effector memory phenotype. CD4(+) CD39(+) single- cell RNA-sequenced TILs shared similar well-known activation, tissue residency, and effector cellassociated genes with CD8(+) CD39(+) CD103(+) TILs. Finally, analysis of directly ex vivo cell-sorted and in vitro expanded pure populations of CD39-positive and negative CD4(+) and CD8(+) TILs revealed that tumor-specific antigen reactivity was almost exclusively detected among CD39(+) cells. Immunotherapy of cancer is based on the activation of tumor-reactive CD4(+) and CD8(+) T cells. We show that the expression of CD39 can be used to identify, isolate, and expand tumor-reactive T-cell populations in cancers.

Date issued
2020-10-01
Language
English
Publisher
AMER ASSOC CANCER RESEARCH
Is part of
Cancer Immunology Research (2020), Vol. 8, no. 10, p. 1311-1321
hdl
1887/3182295
doi
10.1158/2326-6066.CIR-20-0270