PT  - JOURNAL ARTICLE
AU  - Jin, Hyung-seung
AU  - Ko, Minkyung
AU  - Choi, Da-som
AU  - Kim, June Hyuck
AU  - Lee, Dong-hee
AU  - Kang, Seong-Ho
AU  - Kim, Inki
AU  - Lee, Hee Jin
AU  - Choi, Eun Kyung
AU  - Kim, Kyu-pyo
AU  - Yoo, Changhoon
AU  - Park, Yoon
TI  - CD226<sup>hi</sup>CD8<sup>+</sup> T Cells Are a Prerequisite for Anti-TIGIT Immunotherapy
AID  - 10.1158/2326-6066.CIR-19-0877
DP  - 2020 Jul 01
TA  - Cancer Immunology Research
PG  - 912--925
VI  - 8
IP  - 7
4099  - http://cancerimmunolres.aacrjournals.org/content/8/7/912.short
4100  - http://cancerimmunolres.aacrjournals.org/content/8/7/912.full
SO  - Cancer Immunol Res2020 Jul 01; 8
AB  - 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 CD226loCD8+ T cells accumulate at the tumor site and have an exhausted phenotype with impaired functionality. In contrast, CD226hiCD8+ tumor-infiltrating T cells possess greater self-renewal capacity and responsiveness. Anti-TIGIT treatment selectively affects CD226hiCD8+ 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 CD226hiCD8+ 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 CD226hiCD8+ T cells may improve responses to anti-TIGIT therapy.