期刊
ONCOIMMUNOLOGY
卷 4, 期 2, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/2162402X.2014.977164
关键词
B7-H3; MDSC; non-small cell lung cancer; Treg; Tumor microenvironment
资金
- National Natural Science Foundation of China [81372276, 31320103918, 30930085, 31170866, 31770834]
- National Basic Research Development Program of China (973 program) [2013CB53051]
- Natural Science Foundation of Jiangsu [BK20131158]
Myeloid-derived suppressor cells (MDSC) potently inhibit antitumor immune responses, and thereby promoti tumor progression and metastasis. However, the nature of human tumor-infiltrating MDSC remains poorly characterized. Here, we find B7-H3 is exclusively expressed on a subset of intratumoral CD14(+)HLA-DR-/low MDSC but absent from adjacent normal lung tissues of patients with non-small cell lung carcinoma (NSCLC). Cytokine analysis revealed that B7-H3(+)CD14(+)HLA-DR-/low MDSC (B7-H3(+)MDSC) produced higher levels of IL-10 and TNF alpha but lower levels of IL-1 beta and IL-6 when compared with B7-H3(+)CD14(+)HLA-DR-/low myeloid-derived suppressor cells (B7-H3(+)MDSC). In a murine lung cancer model, B7-H3(+)MDSCs were found only in the tumor microenvironment and their frequencies increased during tumor progression. Clinical data analysis indicated that a higher frequency of B7-H3(+)MDSCs was associated with reduced recurrence-free survival in patients with NSCLC. Taken together, we identify a novel subset of MDSCs within the tumor microenvironment that fosters tumor progression.
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