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

Mao,Yong; Chen,Lujun; Wang,Fengming; Zhu,Dawei; Ge,Xiaosong; Hua,Dong; Sun,Jing

doi:10.3892/ol.2017.6935

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

Authors:
- Yong Mao
- Lujun Chen
- Fengming Wang
- Dawei Zhu
- Xiaosong Ge
- Dong Hua
- Jing Sun
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Affiliations: Department of Oncology, The Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, P.R. China, Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu 213003, P.R. China, Testing Center, Center for Disease Prevention and Control, Changzhou, Jiangsu 213000, P.R. China, Department of Immunology, Medical College of Soochow University, Suzhou, Jiangsu 215123, P.R. China
Published online on: September 14, 2017 https://doi.org/10.3892/ol.2017.6935
Pages: 6177-6183

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Abstract

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.

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