Jin, Hyung-seung Ko, Minkyung Choi, Da-som Kim, June Hyuck Lee, Dong-hee Kang, Seong-Ho Kim, Inki Lee, Hee Jin Choi, Eun Kyung Kim, Kyu-pyo Yoo, Changhoon Park, Yoon 2024-01-19T17:04:17Z 2024-01-19T17:04:17Z 2021-09-05 2020-07 2326-6066 https://pubs.kist.re.kr/handle/201004/118446 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(lo)CD8(+) T cells accumulate at the tumor site and have an exhausted phenotype with impaired functionality. In contrast, CD226(hi)CD8(+) tumor-infiltrating T cells possess greater self-renewal capacity and responsiveness. Anti-TIGIT treatment selectively affects CD226(hi)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(hi)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(hi)CD8(+) T cells may improve responses to anti-TIGIT therapy. English AMER ASSOC CANCER RESEARCH IMMUNE-RESPONSE ACTIVATION EXHAUSTION RECRUITMENT CD226 AXIS CD226(hi)CD8(+) T Cells Are a Prerequisite for Anti-TIGIT Immunotherapy Article 10.1158/2326-6066.CIR-19-0877 1 CANCER IMMUNOLOGY RESEARCH, v.8, no.7, pp.912 - 925 CANCER IMMUNOLOGY RESEARCH 8 7 912 925 scie scopus 000546010400007 2-s2.0-85087469656 Oncology Immunology Oncology Immunology Article IMMUNE-RESPONSE ACTIVATION EXHAUSTION RECRUITMENT CD226 AXIS