Late-stage tumors induce anemia and immunosuppressive extramedullary erythroid progenitor cells.
Late-stage tumors induce anemia and immunosuppressive extramedullary erythroid progenitor cells.
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晚期肿瘤诱发贫血和免疫抑制髓外红系祖细胞
DOI：
10.1038/s41591-018-0205-5
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发表时间：
2018-10
期刊：
影响因子：
82.9
通讯作者：
Zhu B
中科院分区：
文献类型：
--
作者：
Zhao L;He R;Long H;Guo B;Jia Q;Qin D;Liu SQ;Wang Z;Xiang T;Zhang J;Tan Y;Huang J;Chen J;Wang F;Xiao M;Gao J;Yang X;Zeng H;Wang X;Hu C;Alexander PB;Symonds ALJ;Yu J;Wan Y;Li QJ;Ye L;Zhu B
晚期癌症患者的免疫力受损不仅限于抗肿瘤反应，如疫苗接种保护性差和对感染的高度易感性所证明的。这在很大程度上归因于化疗诱导的先天免疫损伤，如中性粒细胞减少症，而肿瘤对造血和过继免疫的全身作用仍不完全清楚。在这里，我们观察到贫血与严重缺乏CD8+ T细胞对病原体的反应在未经治疗的小鼠携带大肿瘤。具体地说，我们鉴定了CD45+红系祖细胞（CD71+TER119+，EPCs）作为稳健的免疫抑制剂。由肿瘤生长相关的髓外造血诱导的CD45+EPCs在脾脏中积累成为主要群体，其数量超过调节性T细胞（TCFs）和髓源性抑制细胞（MDSC）。CD45+ EPC转录组与MDSC非常相似，并且与MDSC一样，活性氧物质的产生是CD45+ EPC介导的免疫抑制的主要机制。类似地，在贫血的癌症患者中检测到免疫抑制性CD45+ EPC群体。这些发现确定了一个主要的免疫抑制细胞群体，可能有助于在晚期癌症患者中常见的受损T细胞反应。
Impaired immunity in late stage cancer patients is not limited to anti-tumor responses, as demonstrated by poor vaccination protection and high susceptibility to infection. This has been largely attributed to chemotherapy-induced impairment of innate immunity such as neutropenia, whereas systemic effects of tumors on hematopoiesis and adoptive immunity remain incompletely understood. Here we observed anemia associated with severe deficiency of CD8+ T cell responses against pathogens in treatment-naïve mice bearing large tumors. Specifically, we identify CD45+ erythroid progenitor cells (CD71+TER119+, EPCs) as robust immunosuppressors. CD45+EPCs, induced by tumor growth-associated extramedullary hematopoiesis, accumulate in the spleen to become a major population, outnumbering regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). The CD45+ EPC transcriptome closely resembles that of MDSCs, and, like MDSCs, reactive oxygen species production is a major mechanism underlying CD45+ EPC-mediated immunosuppression. Similarly, an immunosuppressive CD45+ EPC population was detected in cancer patients with anemia. These findings identify a major population of immunosuppressive cells that likely contributes to the impaired T cell responses commonly observed in advanced cancer patients.
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影响因子：
64.8
作者：
Inra CN;Zhou BO;Acar M;Murphy MM;Richardson J;Zhao Z;Morrison SJ
通讯作者：
Morrison SJ
影响因子：
8.8
作者：
Ugel, Stefano;Peranzoni, Elisa;Bronte, Vincenzo
通讯作者：
Bronte, Vincenzo
肿瘤诱导的脾成红细胞样 Ter 细胞的产生促进肿瘤进展
影响因子：
64.5
作者：
Han, Yanmei;Liu, Qiuyan;Cao, Xuetao
通讯作者：
Cao, Xuetao
影响因子：
32.4
作者：
Zhang B;Liu SQ;Li C;Lykken E;Jiang S;Wong E;Gong Z;Tao Z;Zhu B;Wan Y;Li QJ
通讯作者：
Li QJ
影响因子：
30.5
作者：
Jackson, SH;Devadas, S;Williams, MS
通讯作者：
Williams, MS