Increased IFNγ + T Cells Are Responsible for the Clinical Responses of Low-Dose DNA-Demethylating Agent Decitabine Antitumor Therapy.

Purpose: Low-dose DNA-demethylating agent decitabine therapy is effective in a subgroup of cancer patients. It remains largely elusive for the biomarker to predict therapeutic response and the underlying antitumor mechanisms, especially the impact on host antitumor immunity. Experimental Design: The influence of low-dose decitabine on T cells was detected both in vitro and in vivo. Moreover, a test cohort and a validation cohort of advanced solid tumor patients with low-dose decitabine-based treatment were involved. The activation, proliferation, polarization, and cytolysis capacity of CD3(+)T cells were analyzed by FACS and CCK8 assay. KaplanMeier and Cox proportional hazard regression analysis were performed to investigate the prognostic value of enhanced T-cell activity following decitabine epigenetic therapy. Results: Low-dose decitabine therapy enhanced the activation and proliferation of human IFN gamma(+) T cells, promoted Th1 polarization and activity of cytotoxic T cells both in vivo and in vitro, which in turn inhibited cancer progression and augmented the clinical effects of patients. In clinical trials, increased IFN gamma T+ cells and increased T-cell cytotoxicity predicted improved therapeutic responses and survival in the test cohort and validation cohort. Conclusions: We find that low-dose decitabine therapy promotes antitumor T-cell responses by promoting T-cell proliferation and the increased IFN gamma(+) T cells may act as a potential prognostic biomarker for the response to decitabine- based antitumor therapy. (C)2017 AACR.