Qu Qiu-Xia, Huang Qin, Shen Yu, Zhu Yi-Bei, Zhang Xue-Guang
Clinical Immunology Institute, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, People's Republic of China.
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, China.
Tumour Biol. 2016 Apr;37(4):5031-7. doi: 10.1007/s13277-015-4066-y. Epub 2015 Nov 6.
Tumor-associated macrophages (TAMs) have been characterized as a critical population of immunosuppressive cells in a variety of tumor types. PD-L1 (also termed B7-H1) has been described to exert co-inhibitory and immune regulatory functions. Here, in ovarian cancer, PD-L1 is selectively overexpressed on some TAM compared that of benign ovarian disease. When expanding the data in peripheral blood, the proportion of PD-L1(+)CD68(+) cell among CD68(+) cells and the intensity of PD-L1 staining on CD68(+) cell in healthy group were similar to that observed in ovarian cyst group; instead, these two measures were significantly higher in ovarian cancer group, thereafter related to TNM stage. Interestingly, intracellular levels of IL-10, IL-6, TNF-α, and IFN-γ in PD-L1(+)CD68(+) macrophage were higher than those in PD-L1(-)CD68(+) macrophage, especially IL-6 expression. Based on the PD-L1 receptor PD-1 expression on tumor-infiltrating cytotoxic cells, our data supported that expression of PD-L1 on TAM promoted apoptosis of T cells via interaction with PD-1 on CD8(+)T cells. Taken together, these results suggested that PD-L1-expressing macrophage represents a novel suppressor cell population in ovarian cancer, which contributes immune escape of ovarian cancer.
肿瘤相关巨噬细胞(TAM)已被确定为多种肿瘤类型中免疫抑制细胞的关键群体。PD-L1(也称为B7-H1)已被描述具有共抑制和免疫调节功能。在此,在卵巢癌中,与良性卵巢疾病相比,PD-L1在一些TAM上选择性过表达。当在外周血中扩展数据时,健康组中CD68(+)细胞中PD-L1(+)CD68(+)细胞的比例以及CD68(+)细胞上PD-L1染色的强度与卵巢囊肿组中观察到的相似;相反,这两项指标在卵巢癌组中显著更高,并且与TNM分期相关。有趣的是,PD-L1(+)CD68(+)巨噬细胞中IL-10、IL-6、TNF-α和IFN-γ的细胞内水平高于PD-L1(-)CD68(+)巨噬细胞,尤其是IL-6的表达。基于肿瘤浸润性细胞毒性细胞上PD-L1受体PD-1的表达,我们的数据支持TAM上PD-L1的表达通过与CD8(+)T细胞上的PD-1相互作用促进T细胞凋亡。综上所述,这些结果表明表达PD-L1的巨噬细胞代表卵巢癌中一种新的抑制细胞群体,其促成了卵巢癌的免疫逃逸。