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CD226 hi CD8 + T Cells Are a Prerequisite for Anti-TIGIT Immunotherapy
Ist Teil von
Cancer immunology research, 2020-07, Vol.8 (7), p.912
Ort / Verlag
United States
Erscheinungsjahr
2020
Quelle
MEDLINE
Beschreibungen/Notizen
Clinical trials are evaluating the efficacy of anti-TIGIT for use as single-agent therapy or in combination with programmed death 1 (PD-1)/programmed death-ligand 1 blockade. How and whether a TIGIT blockade will synergize with immunotherapies is not clear. Here, we show that CD226
CD8
T cells accumulate at the tumor site and have an exhausted phenotype with impaired functionality. In contrast, CD226
CD8
tumor-infiltrating T cells possess greater self-renewal capacity and responsiveness. Anti-TIGIT treatment selectively affects CD226
CD8
T cells by promoting CD226 phosphorylation at tyrosine 322. CD226 agonist antibody-mediated activation of CD226 augments the effect of TIGIT blockade on CD8
T-cell responses. Finally, mFOLFIRINOX treatment, which increases CD226
CD8
T cells in patients with pancreatic ductal adenocarcinoma, potentiates the effects of TIGIT or PD-1 blockade. Our results implicate CD226 as a predictive biomarker for cancer immunotherapy and suggest that increasing numbers of CD226
CD8
T cells may improve responses to anti-TIGIT therapy.