The increase of circulating PD-L1-expressing CD68+ macrophage in ovarian cancer
The increase of circulating PD-L1-expressing CD68+ macrophage in ovarian cancer
复制标题
卵巢癌中循环表达 PD-L1 的 CD68 巨噬细胞增加
作者：
Qiu;Qin Huang;Yu Shen;Yi;Xue
肿瘤相关巨噬细胞（TAM）已被定性为多种肿瘤类型中关键的免疫抑制细胞群。 PD-L1（也称为 B7-H1）已被描述为发挥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 在某些 TAM 上选择性过度表达。扩大外周血数据，健康组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相似；相反，这两项指标在卵巢癌组中显着较高，随后与 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表达。基于肿瘤浸润细胞毒性细胞上的 PD-L1 受体 PD-1 表达，我们的数据支持 TAM 上的 PD-L1 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 的巨噬细胞代表了卵巢癌中的一种新型抑制细胞群，有助于卵巢癌的免疫逃逸。
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.
DOI：
10.1056/nejmoa1200694
发表时间：
2012-06-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Brahmer JR;Tykodi SS;Chow LQ;Hwu WJ;Topalian SL;Hwu P;Drake CG;Camacho LH;Kauh J;Odunsi K;Pitot HC;Hamid O;Bhatia S;Martins R;Eaton K;Chen S;Salay TM;Alaparthy S;Grosso JF;Korman AJ;Parker SM;Agrawal S;Goldberg SM;Pardoll DM;Gupta A;Wigginton JM
通讯作者：
Wigginton JM
影响因子：
11.2
作者：
Duraiswamy J;Freeman GJ;Coukos G
通讯作者：
Coukos G
DOI：
10.1056/nejmoa1200690
发表时间：
2012-06-28
期刊：
The New England journal of medicine
影响因子：
--
作者：
Topalian SL;Hodi FS;Brahmer JR;Gettinger SN;Smith DC;McDermott DF;Powderly JD;Carvajal RD;Sosman JA;Atkins MB;Leming PD;Spigel DR;Antonia SJ;Horn L;Drake CG;Pardoll DM;Chen L;Sharfman WH;Anders RA;Taube JM;McMiller TL;Xu H;Korman AJ;Jure-Kunkel M;Agrawal S;McDonald D;Kollia GD;Gupta A;Wigginton JM;Sznol M
通讯作者：
Sznol M