Details

Autor(en) / Beteiligte

• 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

Titel

CD226hiCD8+ T Cells Are a Prerequisite for Anti-TIGIT Immunotherapy

Ist Teil von

• Cancer immunology research, 2020-07, Vol.8 (7), p.912-925

Erscheinungsjahr

2020

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• Abstract 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.