Zhang Guangbo, Huang Haitao, Zhu Yibei, Yu Gehua, Gao Xin, Xu Yunyun, Liu Cuiping, Hou Jianquan, Zhang Xueguang
Clinical Immunology Laboratory; Soochow University ; Suzhou, China ; Institute of Medical Biotechnology; Soochow University ; Suzhou, China.
Institute of Medical Biotechnology; Soochow University ; Suzhou, China ; Department of Thoracic Surgery; The First Affiliated Hospital of Soochow University ; Suzhou, China.
Oncoimmunology. 2015 Mar 6;4(2):e977164. doi: 10.4161/2162402X.2014.977164. eCollection 2015 Feb.
Myeloid-derived suppressor cells (MDSC) potently inhibit antitumor immune responses, and thereby promoti tumor progression and metastasis. However, the nature of human tumor-infiltrating MDSC remains poorly characterized. Here, we find B7-H3 is exclusively expressed on a subset of intratumoral CD14HLA-DR MDSC but absent from adjacent normal lung tissues of patients with non-small cell lung carcinoma (NSCLC). Cytokine analysis revealed that B7-H3CD14HLA-DR MDSC (B7-H3MDSC) produced higher levels of IL-10 and TNFα but lower levels of IL-1β and IL-6 when compared with B7-H3CD14HLA-DR myeloid-derived suppressor cells (B7-H3MDSC). In a murine lung cancer model, B7-H3MDSCs were found only in the tumor microenvironment and their frequencies increased during tumor progression. Clinical data analysis indicated that a higher frequency of B7-H3MDSCs was associated with reduced recurrence-free survival in patients with NSCLC. Taken together, we identify a novel subset of MDSCs within the tumor microenvironment that fosters tumor progression.
髓源性抑制细胞（MDSC）可有效抑制抗肿瘤免疫反应，从而促进肿瘤进展和转移。然而，人类肿瘤浸润性MDSC的特性仍未得到充分表征。在此，我们发现B7-H3仅在肿瘤内CD14 HLA-DR MDSC的一个亚群上表达，而在非小细胞肺癌（NSCLC）患者的相邻正常肺组织中不存在。细胞因子分析显示，与B7-H3 CD14 HLA-DR髓源性抑制细胞（B7-H3 MDSC）相比，B7-H3 CD14 HLA-DR MDSC（B7-H3 MDSC）产生更高水平的IL-10和TNFα，但产生更低水平的IL-1β和IL-6。在小鼠肺癌模型中，仅在肿瘤微环境中发现B7-H3 MDSCs，并且它们的频率在肿瘤进展过程中增加。临床数据分析表明，B7-H3 MDSCs的较高频率与NSCLC患者无复发生存率降低相关。综上所述，我们在肿瘤微环境中鉴定出一个促进肿瘤进展的新型MDSC亚群。
