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Blood, 15 August 2008, Vol. 112, No. 4, pp. 1269-1279.
Prepublished online as a Blood First Edition Paper on June 4, 2008; DOI 10.1182/blood-2008-03-147033.
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Submitted March 24, 2008
Accepted May 14, 2008
SCF-mediated mast cell infiltration and activation exacerbate the inflammation and immunosuppression in tumor microenvironment
Bo Huang, Zhang Lei, Gui-Mei Zhang, Dong Li, Chuanwang Song, Bo Li, Yanyan Liu, Ye Yuan, Jay Unkeless, Huabao Xiong, and Zuo-Hua Feng*
Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China
Immunology Institute, Mount Sinai School of Medicine, New York, United States
* Corresponding author; email: fengzhg{at}public.wh.hb.cn.
Despite the evidence for the role of inflammation in cancer initiation, promotion, and progression, the precise mechanism by which the inflammation within tumor is orchestrated by inflammatory cells remains to be determined. Here we report that tumor-infiltrating mast cells remodel tumor microenvironment and promote tumor growth. Mast cell infiltration and activation in tumor were mainly mediated by tumor-derived stem cell factor (SCF) and its receptor c-Kit on mast cells. Low concentration of SCF efficiently induced the chemotactic migration of mast cells. Tumor-infiltrating mast cells, activated by higher concentration of SCF, expressed multiple proinflammatory factors and increased IL-17 expression in tumor. The activity of NF- B and AP-1 in tumor cells was intensified in mast cell-remodeled inflammatory microenvironment. SCF-activated mast cells also exacerbated tumor immunosuppression by releasing adenosine and increasing Treg cells, which augmented the suppression of T cells and NK cells in tumor. These findings emphasize that the remodeling of tumor microenvironment can actually be initiated by tumor cell-released SCF, and suggest that mast cell is not only a participator but also a critical regulator of inflammation and immunosuppression in tumor microenvironment.
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