Non-conventional Inhibitory CD4⁺Foxp3^-PD-1^hi T Cells as a Biomarker of Immune Checkpoint Blockade Activity.

ABSTRACT: A significant proportion of cancer patients do not respond to immune checkpoint blockade. To better understand the molecular mechanisms underlying these treatments, we explored the role of CD4⁺Foxp3^- T cells expressing PD-1 (4PD1^hi) and observed that 4PD1^hi accumulate intratumorally as a function of tumor burden. Interestingly, CTLA-4 blockade promotes intratumoral and peripheral 4PD1^hi increases in a dose-dependent manner, while combination with PD-1 blockade mitigates this effect and improves anti-tumor activity. We found that lack of effective 4PD1^hi reduction after anti-PD-1 correlates with poor prognosis. Mechanistically, we provide evidence that mouse and human circulating and intra-tumor 4PD1^hi inhibit T ce

SUBMITTER: Zappasodi R 

PROVIDER: S-EPMC6648657 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature