CXCR2-expressing myeloid-derived suppressor cells are essential to promote colitis-associated tumorigenesis.

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.

journal_name

Cancer Cell

journal_title

Cancer cell

authors

Katoh H,Wang D,Daikoku T,Sun H,Dey SK,Dubois RN

doi

10.1016/j.ccr.2013.10.009

subject

Has Abstract

pub_date

2013-11-11 00:00:00

pages

631-44

issue

5

eissn

1535-6108

issn

1878-3686

pii

S1535-6108(13)00457-1

journal_volume

24

pub_type

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