Page 24 - M. Immunology

[M. Immunology-18]

TIGIT blockade enhances T cell activation via tyrosine

phosphorylation of CD226

Minkyung Ko¹, Da-som Choi², June Hyuck Kim¹, Dong-hee Lee², Hyun Kyu Song³, Hyung-seung Jin²˙*,
Yoon Park¹˙*

¹Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Seoul

02792, South Korea, ²Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center,
University of Ulsan College of Medicine, Seoul 05505, South Korea, ³Department of Life Sciences, Korea University,
Seoul 02841, Republic of Korea

Multiple clinical trials are evaluating the efficacy of anti-TIGIT antibodies for use as single-agent therapy or in
combination with PD-1/PD-L1 blockade. However, TIGIT’s mechanism of action and whether a TIGIT blockade will

synergize with current immunotherapies is not fully understood. Here we show that CD226loCD8+ T cells are
accumulated at the tumor site and have an exhausted phenotype with an impaired functionality. In contrast,

CD226hiCD8+ tumor-infiltrating T cells possess a higher self-renewal capacity and potent responsiveness. Anti-TIGIT
antibody 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. Our results implicate CD226 as a predictive biomarker for cancer immunotherapy and suggest that

increasing CD226hiCD8+ T cells may improve anti-TIGIT therapy.