CXCR2-Expressing Myeloid-Derived Suppressor Cells Are Essential to Promote Colitis-Associated Tumorigenesis

Hiroshi Katoh; Dingzhi Wang; Takiko Daikoku; Haiyan Sun; Sudhansu K. Dey; Raymond N. DuBois

doi:10.1016/j.ccr.2013.10.009

CXCR2-Expressing Myeloid-Derived Suppressor Cells Are Essential to Promote Colitis-Associated Tumorigenesis

Hiroshi Katoh, Dingzhi Wang, Takiko Daikoku, Haiyan Sun, Sudhansu K. Dey, Raymond N. DuBois

Research output: Contribution to journal › Article › peer-review

322 Scopus citations

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⁺ Tcell cytotoxic activity.

Original language	English (US)
Pages (from-to)	631-644
Number of pages	14
Journal	Cancer cell
Volume	24
Issue number	5
DOIs	https://doi.org/10.1016/j.ccr.2013.10.009
State	Published - Nov 11 2013

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

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10.1016/j.ccr.2013.10.009

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title = "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+ Tcell cytotoxic activity.",

author = "Hiroshi Katoh and Dingzhi Wang and Takiko Daikoku and Haiyan Sun and Dey, {Sudhansu K.} and DuBois, {Raymond N.}",

note = "Funding Information: This work is supported, in part, by NIH MERIT awards R37 DK47297, RO1 DK 62112, NCI, P01 CA77839, and CPRIT RP100960. We thank the National Colorectal Cancer Research Alliance for its generous support (to R.N.D.) and the Uehara Memorial Foundation Research Fellowship (to H.K.). We thank Drs. Sun-Hee Kim, Yuchen Du, and Vijaykumar R. Holla for help with experimental methods. We also thank Drs. Sandra S. Ojeda and Kimberly S. Schluns for providing the protocol of colonic immunocyte extraction. We are grateful to Nalini Patel, Wendy Schober, and Duncan Mak at the Flow Cytometry Core Facility of MD Anderson Cancer Center for their assistance conducting analysis of flow cytometry. ",

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AU - Katoh, Hiroshi

AU - Wang, Dingzhi

AU - Daikoku, Takiko

AU - Sun, Haiyan

AU - Dey, Sudhansu K.

AU - DuBois, Raymond N.

N1 - Funding Information: This work is supported, in part, by NIH MERIT awards R37 DK47297, RO1 DK 62112, NCI, P01 CA77839, and CPRIT RP100960. We thank the National Colorectal Cancer Research Alliance for its generous support (to R.N.D.) and the Uehara Memorial Foundation Research Fellowship (to H.K.). We thank Drs. Sun-Hee Kim, Yuchen Du, and Vijaykumar R. Holla for help with experimental methods. We also thank Drs. Sandra S. Ojeda and Kimberly S. Schluns for providing the protocol of colonic immunocyte extraction. We are grateful to Nalini Patel, Wendy Schober, and Duncan Mak at the Flow Cytometry Core Facility of MD Anderson Cancer Center for their assistance conducting analysis of flow cytometry.

PY - 2013/11/11

Y1 - 2013/11/11

N2 - 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+ Tcell cytotoxic activity.

AB - 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+ Tcell cytotoxic activity.

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CXCR2-Expressing Myeloid-Derived Suppressor Cells Are Essential to Promote Colitis-Associated Tumorigenesis

Abstract

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