Cancer cell-expressed B7-H3 regulates the differentiation of tumor-associated macrophages in human colorectal carcinoma

被引：73
作者：
Mao, Yong [1 ,2 ]
Chen, Lujun [3 ]
Wang, Fengming [4 ]
Zhu, Dawei [3 ]
Ge, Xiaosong [1 ]
Hua, Dong [1 ,2 ]
Sun, Jing [5 ]
机构：
[1] Jiangnan Univ, Affiliated Hosp, Dept Oncol, 200 Huihe Rd, Wuxi 214062, Jiangsu, Peoples R China
[2] Fourth Hosp Wuxi, Dept Immunol, Wuxi 214062, Jiangsu, Peoples R China
[3] Soochow Univ, Affiliated Hosp 3, Dept Tumor Biol Treatment, Changzhou 213003, Jiangsu, Peoples R China
[4] Ctr Dis Prevent & Control, Testing Ctr, Changzhou 213000, Jiangsu, Peoples R China
[5] Soochow Univ, Med Coll, Dept Immunol, 199 Renai Rd, Suzhou 215123, Jiangsu, Peoples R China
来源：
ONCOLOGY LETTERS | 2017年 / 14卷 / 05期
基金：
中国国家自然科学基金;
关键词：
B7-H3; colorectal carcinoma; tumor-associated macrophage; differentiation; T-CELLS; ANTICANCER THERAPY; UP-REGULATION; PROGRESSION; ACTIVATION; MICROENVIRONMENTS; POLARIZATION; DYSFUNCTION; POPULATION; RESPONSES;
D O I：
10.3892/ol.2017.6935
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Co-stimulatory molecule B7 homolog 3 protein (B7-H3) has been described as an important tumor antigen in various human tumors. The exact role of B7-H3 in tumor progression and its receptor are still ambiguous. The phenotype and the function of tumor-associated macrophages (TAMs) in human solid tumors are complicated and could contribute to the shaping of the tumor microenvironment. In the present study, B7-H3 expression and lymphocyte infiltration were investigated by immunohistochemistry in 117 colorectal carcinoma (CRC) patients. B7-H3 expression was positively associated with the infiltrating density of macrophage in CRC tissues, and B7-H3 expression and the infiltrating density of macrophages were negatively associated with the overall survival rate of patients. The putative B7-H3 receptor was found on activated monocytes and macrophages, indicating the direct function of B7-H3 signal on macrophages. Additional results revealed that during the differentiation of TAMs, B7-H3 promoted the polarization of type 2 macrophages (M2s) and switch of the M1 phenotype to the M2 phenotype. Thus, B7-H3 signaling promotes M2 differentiation via the putative receptor on monocytes and macrophages. Targeting the manipulation of TAMs through the B7-H3 pathway may be valuable for the development of novel immunotherapeutic strategies against human CRC.
引用
收藏
页码：6177 / 6183
页数：7
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