CXCR2-expressing Myeloid-derived Suppressor Cells Are Essential to Promote Colitis-associated Tumorigenesis

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2013 Nov 16

PMID 24229710

Citations 297

Authors

Hiroshi Katoh

Dingzhi Wang

Takiko Daikoku

Haiyan Sun

Sudhansu K Dey

Raymond N DuBois

Affiliations

Soon will be listed here.

Abstract

A large body of evidence indicates that chronic inflammation is one of several key risk factors for cancer initiation, progression, and metastasis. However, the underlying mechanisms responsible for the contribution of inflammation and inflammatory mediators to cancer remain elusive. Here, we present genetic evidence that loss of CXCR2 dramatically suppresses chronic colonic inflammation and colitis-associated tumorigenesis through inhibiting infiltration of myeloid-derived suppressor cells (MDSCs) into colonic mucosa and tumors in a mouse model of colitis-associated cancer. CXCR2 ligands were elevated in inflamed colonic mucosa and tumors and induced MDSC chemotaxis. Adoptive transfer of wild-type MDSCs into Cxcr2(-/-) mice restored AOM/DSS-induced tumor progression. MDSCs accelerated tumor growth by inhibiting CD8(+) T cell cytotoxic activity.

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