Intratumoral CD45+CD71+ erythroid cells induce immune tolerance and predict tumor recurrence in hepatocellular carcinoma
Intratumoral CD45+CD71+ erythroid cells induce immune tolerance and predict tumor recurrence in hepatocellular carcinoma
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DOI：
10.1016/j.canlet.2020.12.003
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发表时间：
2021-02-28
期刊：
影响因子：
9.7
通讯作者：
Wu, Xiang-Yuan
中科院分区：
文献类型：
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作者：
Chen, Jie;Qiao, Yi-Dan;Wu, Xiang-Yuan
近年来研究发现，脾脏髓外红细胞生成过程中产生的CD 45（+）CD 71（+）红系细胞可抑制新生儿和成人恶性肿瘤患者的抗感染和肿瘤免疫功能。然而，它们在肿瘤微环境中的作用尚未研究。在本研究中，我们发现，在肝细胞癌（HCC）组织中的CD 45（+）CD 71（+）红系细胞的数量显著高于癌旁区域和循环。此外，与一些免疫抑制细胞以及CD 45（-）CD 71（+）红系细胞相比，它们在HCC组织中更丰富。CD 45（+）CD 71（+）红系细胞通过旁分泌和细胞-细胞接触方式产生活性氧、IL-10和TGF-β抑制T细胞，其抑制作用强于髓系来源的抑制细胞。通过免疫荧光显示，肿瘤组织中CD 45（+）CD 71（+）红系细胞的丰度可预测无病生存期和总生存期，其预后价值优于肝癌意大利计划评分。本研究表明，肝癌组织中CD 45（+）CD 71（+）红系细胞的聚集在肿瘤微环境中可能发挥上级免疫抑制作用，并可能作为预测肝癌复发的有价值的生物标志物。
CD45(+)CD71(+) erythroid cells generated through splenic extramedullary erythropoiesis have recently been found to suppress anti-infection and tumor immunity in neonates and adults with malignances. However, their role in tumor microenvironment has not been investigated. In the present study, we found that the number of CD45(+)CD71(+) erythroid cells was significantly elevated in hepatocellular carcinoma (HCC) tissues compared to that in paratumor region and circulation. Additionally, they were more abundant in HCC tissues compared to some immune suppressive cells as well as CD45(-)CD71(+) erythroid cells. CD45(+)CD71(+) erythroid cells suppressed T cells through generation of reactive oxygen species, IL-10, and TGF-beta in a paracrine and cell-cell contact manner, and their suppressive effect was stronger than that of myeloid-derived suppressor cells. The abundance of CD45(+)CD71(+) erythroid cells in tumor tissue, as illustrated via immunofluorescence, predicted disease-free survival and overall survival, and its prognostic value was better than that of Cancer of the Liver Italian Program score. This study demonstrated that accumulation of intratumoral CD45(+)CD71(+) erythroid cells in HCC tissues could play a superior immunosuppressive role in tumor microenvironment and may serve as a valuable biomarker to predict recurrence of HCC.