Cancer immunology research, 2020-07, Vol.8 (7), p.912
2020
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Details
- Autor(en) / Beteiligte
- Titel
- CD226 hi CD8 + T Cells Are a Prerequisite for Anti-TIGIT Immunotherapy
- Ist Teil von
- Cancer immunology research, 2020-07, Vol.8 (7), p.912
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2020
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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 CD8 T cells accumulate at the tumor site and have an exhausted phenotype with impaired functionality. In contrast, CD226 CD8 tumor-infiltrating T cells possess greater self-renewal capacity and responsiveness. Anti-TIGIT treatment selectively affects CD226 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 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 CD8 T cells may improve responses to anti-TIGIT therapy.
- Sprache
- Englisch
- Identifikatoren
- eISSN: 2326-6074Titel-ID: cdi_pubmed_primary_32265229
- Format
- –
- Schlagworte
- Animals, Antigens, Differentiation, T-Lymphocyte - immunology, Antigens, Differentiation, T-Lymphocyte - metabolism, Antineoplastic Agents, Immunological - pharmacology, Biomarkers, Tumor - immunology, Biomarkers, Tumor - metabolism, CD8-Positive T-Lymphocytes - immunology, CD8-Positive T-Lymphocytes - metabolism, Cell Line, Tumor, Disease Models, Animal, Female, Humans, Immunotherapy - methods, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Neoplasms - immunology, Neoplasms - metabolism, Neoplasms - therapy, Receptors, Immunologic - antagonists & inhibitors, Receptors, Immunologic - immunology