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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
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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
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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
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Journal Article
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
2017
Overview
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 suppress the growth of xenografts in nude mice, and this inhibition of tumor growth was completely abrogated by NK depletion. These findings strongly suggested that PD-1 is an inhibitory regulator of NK cells in digestive cancers. PD-1 blockade might be an efficient strategy in NK cell-based tumor immunotherapy.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
1-Phosphatidylinositol 3-kinase
/ Animals
/ B7-H1 Antigen - antagonists & inhibitors
/ Cancer
/ Cell Proliferation - drug effects
/ Female
/ Gastrointestinal Neoplasms - immunology
/ Gastrointestinal Neoplasms - pathology
/ Gastrointestinal Neoplasms - therapy
/ Gene Expression Regulation, Neoplastic
/ Humans
/ Killer Cells, Natural - drug effects
/ Killer Cells, Natural - immunology
/ Liver
/ Male
/ Medicine
/ Mice
/ Oncology
/ Original
/ Programmed Cell Death 1 Receptor - antagonists & inhibitors
/ Programmed Cell Death 1 Receptor - immunology
/ Proteins
/ T cells
/ Tumors
