High-salt Diet Mediates Interplay Between NK Cells and Gut Microbiota to Induce Potent Tumor Immunity

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2021 Sep 13

PMID 34516769

Citations 54

Authors

Zaigham Abbas Rizvi

Rajdeep Dalal

Srikanth Sadhu

Yashwant Kumar

Shakti Kumar

Sonu Kumar Gupta

Manas Ranjan Tripathy

Deepak Kumar Rathore

Amit Awasthi

Affiliations

Soon will be listed here.

Abstract

High-salt diet (HSD) modulates effector and regulatory T cell functions and promotes tissue inflammation in autoimmune diseases. However, effects of HSD and its association with gut microbiota in tumor immunity remain undefined. Here, we report that HSD induces natural killer (NK) cell–mediated tumor immunity by inhibiting PD-1 expression while enhancing IFNγ and serum hippurate. Salt enhanced tumor immunity when combined with a suboptimal dose of anti-PD1 antibody. While HSD-induced tumor immunity was blunted upon gut microbiota depletion, fecal microbiota transplantation (FMT) from HSD mice restored the tumor immunity associated with NK cell functions. HSD increased the abundance of and caused increased gut permeability leading to intratumor localization of , which enhanced NK cell functions and tumor regression. Intratumoral injections of activated NK cells, which inhibited tumor growth. These results indicate that HSD modulates gut microbiome that induces NK cell–dependent tumor immunity with a potential translational perspective.

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