A novel role of hematopoietic CCL5 in promoting triple-negative mammary tumor progression

A novel role of hematopoietic CCL5 in promoting triple-negative mammary tumor progression by

regulating generation of myeloid-derived

suppressor cells

Yan Zhang;Dandan Lv;Ha-Jeong Kim;Robert A Kurt;Wen Bu;Yi Li;Xiaojing Ma

【期刊名称】《细胞研究（英文版）》 【年(卷),期】2013(023)003

【摘要】CCL5 is a member of the CC chemokine family expressed in a wide array of immune and non-immune cells in response to stress signals.CCL5 expression correlates with advanced human breast cancer.However,its functional significance and mode of action have not been established.Here,we show that CCL5-deficient mice are resistant to highly

aggressive,triple-negative

mammary

tumor

growth.Hematopoietic CCL5 is dominant in this phenotype.The absence of hematopoietic CCL5 causes aberrant generation of CD11b+/Gr-1+,myeloid-derived suppressor cells (MDSCs) in the bone marrow in response to tumor growth by accumulating Ly6Chi and Ly6G+ MDSCs with impaired capacity to suppress cytotoxicity of CD8+ T cells.These properties of CCL5 are observed in both orthotopic and spontaneous mammary tumors.Antibody-mediated systemic blockade of CCL5 inhibits tumor progression and enhances the efficacy of therapeutic vaccination against non-immunogenic tumors.CCL5 also helps maintain