| Autor: |
Yoon Park, Changhoon Yoo, Kyu-pyo Kim, Eun Kyung Choi, Hee Jin Lee, Inki Kim, Seong-Ho Kang, Dong-hee Lee, June Hyuck Kim, Da-som Choi, Minkyung Ko, Hyung-seung Jin |
| Rok vydání: |
2023 |
| DOI: |
10.1158/2326-6066.c.6550419.v1 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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