Induced expression of B7-H3 on the lung cancer cells and macrophages suppresses T-cell mediating anti-tumor immune response
Induced expression of B7-H3 on the lung cancer cells and macrophages suppresses T-cell mediating anti-tumor immune response
复制标题
B7-H3 在肺癌细胞和巨噬细胞上的诱导表达抑制 T 细胞介导的抗肿瘤免疫反应
DOI：
10.1016/j.yexcr.2012.09.006
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发表时间：
2013-01-01
影响因子：
3.7
通讯作者：
Huang, Jian-An
中科院分区：
文献类型：
--
作者：
Chen, Cheng;Shen, Yu;Huang, Jian-An
Macrophages are the prominent components of solid tumors and have complex dual functions in their interaction with cancer cells. Strong evidence suggests that TAM is a part of inflammatory circuits that promote tumor progression. B7-homologue 3 (B7-H3), a recently identified homologue of B7.1/2 (CD80/86), has been described to exert co-stimulatory and immune regulatory functions. Here, we showed that a fraction of macrophages in tumor stroma expressed surface B7-H3 molecule. Normal macrophages, which did not express B7-H3, would be induced expressing B7-H3 molecule when culturing with tumor cell. Although a lung cancer cell line constitutively expressed B7-H3 mRNA and protein in plasma, primary tumor cell isolated from the transplanted lung carcinoma model expressed B7-H3 on the surface. Interestingly, in transplanted lung carcinoma model, the expression of membrane-bound B7-H3 in tumor cells was increased as prolonging of tumor transformation. In support, IL-10 released from TAM could stimulate cancer cell expression of membrane bound B7-H3. Furthermore, Lung cancer and TAM-related B7-H3 was identified as a strong inhibitor of T-cell effect and influenced the outcome of T cell immune response. In conclusion, TAM-tumor cell interaction-induced membrane-bound B7-H3 represents a novel immune escape mechanism which links the pro-inflammatory response to immune tolerance in the tumor milieu. (C) 2012 Elsevier Inc. All rights reserved.
