小柯机器人

2022年5月19日，陆军军医大学朱波、美国杜克大学李启靖等研究人员合作在《癌细胞》杂志发表论文，发现肿瘤“挟持”红系前体细胞向髓系细胞分化介导免疫抑制。

研究人员利用对癌症患者和肿瘤小鼠的系谱追踪，证明了红系前体细胞失去了它们的发育潜力，并转换为髓系。单细胞转录组分析显示，尽管红细胞基因表达有数量上的差异，但红细胞分化的髓系细胞（EDMC）在转录上与源自髓系的同类细胞没有区别。EDMC拥有多方面的机制来遏制T细胞介导的抗肿瘤反应。因此，在大多数实体癌中，肿瘤组织内的EDMC含量与T细胞炎症呈负相关；此外，在接受免疫检查点抑制剂（ICI）治疗的各种患者群中，EDMC的富集与贫血表现一致，可预测预后不良。

总之，这些发现揭示了一种前馈机制，肿瘤利用贫血触发的红细胞生成来实现骨髓的转分化和免疫抑制。

据了解，尽管ICI作为抗癌疗法取得了空前的成功，但确定ICI疗效和潜在耐药性的额外机制仍然是一个普遍的临床需求。

附：英文原文

Title: Tumor-induced erythroid precursor-differentiated myeloid cells mediate immunosuppression and curtail anti-PD-1/PD-L1 treatment efficacy

Author: Haixia Long, Qingzhu Jia, Liuyang Wang, Wenfeng Fang, Zhongyu Wang, Tao Jiang, Fei Zhou, Zheng Jin, Jiani Huang, Li Zhou, Chunyan Hu, Xinxin Wang, Jin Zhang, Yujie Ba, Yujie Gong, Xianghua Zeng, Dong Zeng, Xingxing Su, Peter B. Alexander, Li Wang, Limei Wang, Yisong Y. Wan, Xiao-Fan Wang, Li Zhang, Qi-Jing Li, Bo Zhu

Issue&Volume: 2022-05-19

Abstract: Despite the unprecedented success of immune checkpoint inhibitors (ICIs) as anti-cancertherapy, it remains a prevailing clinical need to identify additional mechanisms underlyingICI therapeutic efficacy and potential drug resistance. Here, using lineage trackingin cancer patients and tumor-bearing mice, we demonstrate that erythroid progenitorcells lose their developmental potential and switch to the myeloid lineage. Single-celltranscriptome analyses reveal that, notwithstanding quantitative differences in erythroidgene expression, erythroid differentiated myeloid cells (EDMCs) are transcriptionallyindistinguishable from their myeloid-originated counterparts. EDMCs possess multifacetedmachinery to curtail T cell-mediated anti-tumor responses. Consequently, EDMC contentwithin tumor tissues is negatively associated with T cell inflammation for the majorityof solid cancers; moreover, EDMC enrichment, in accordance with anemia manifestation,is predictive of poor prognosis in various cohorts of patients undergoing ICI therapy.Together, our findings reveal a feedforward mechanism by which tumors exploit anemia-triggerederythropoiesis for myeloid transdifferentiation and immunosuppression.

DOI: 10.1016/j.ccell.2022.04.018

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00211-2

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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