Increased expression of programmed cell death protein 1 on NK cells inhibits NK-cell-mediated anti-tumor function and indicates poor prognosis in digestive cancers.

ABSTRACT: Abnormal expression of activating/inhibitory receptors leads to natural killer (NK) cells dysfunction in tumor. Here we show that programmed cell death protein 1 (PD-1), a well-known immune checkpoint of T cells, is highly expressed on peripheral and tumor-infiltrating NK cells from patients with digestive cancers including esophageal, liver, colorectal, gastric and biliary cancer. The increased PD-1 expression on NK cells indicates poorer survival in esophageal and liver cancers. Blocking PD-1/PD-L1 signaling markedly enhances cytokines production and degranulation and suppresses apoptosis of NK cells in vitro. PD-1/PD-L1 exerts inhibitory effect through repressing the activation of PI3K/AKT signaling in NK cells. More importantly, a PD-1 blocking antibody was found to significantly suppr

SUBMITTER: Liu Y 

PROVIDER: S-EPMC5671935 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature