CXCR2-expressing myeloid-derived suppressor cells are essential to promote colitis-associated tumorigenesis.
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.
Laboratory for Inflammation and Cancer, the Biodesign Institute at Arizona State University, Tempe, AZ 85287, USA.
Hiroshi
H
Katoh
Dingzhi
D
Wang
Takiko
T
Daikoku
Haiyan
H
Sun
Sudhansu K
SK
Dey
Raymond N
RN
Dubois
D019264:Adoptive Transfer; D000818:Animals; D001397:Azoxymethane; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D063646:Carcinogenesis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D054360:Chemokine CXCL1 / Q000502:physiology; D002633:Chemotaxis; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D016264:Dextran Sulfate; D015232:Dinoprostone / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007413:Intestinal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000378:metabolism* / Q000637:transplantation; D023063:Receptors, Interleukin-8B / Q000378:metabolism*; D059016:Tumor Microenvironment
D054360:Chemokine CXCL1; C475895:Cxcl1 protein, mouse; D018836:Inflammation Mediators; D023063:Receptors, Interleukin-8B; D016264:Dextran Sulfate; D015232:Dinoprostone; D001397:Azoxymethane