瑞士肿瘤研究所（IOR）Arianna Calcinotto、Arianna Calcinotto研究组合作发现载脂蛋白E（APOE）诱导前列腺癌中致病性衰老样骨髓细胞。这一研究成果于2023年3月2日发表在国际顶尖学术期刊《癌细胞》上。
他们报告了中性粒细胞亚群的鉴定，这些中性粒细胞上调了细胞衰老标志物的表达并在肿瘤微环境中持续存在。衰老样中性粒细胞表达在骨髓细胞2（TREM2）上表达的触发受体，并且比典型免疫抑制性中性粒细胞更具免疫抑制和促进肿瘤作用。衰老样中性粒细胞的遗传和药理学消除可减少不同前列腺癌小鼠模型中的肿瘤进展。
在机制上，他们发现前列腺肿瘤细胞分泌的APOE结合中性粒细胞上的TREM2，促进其衰老。APOE和TREM2表达在前列腺癌中增加，与预后不良相关。总的来说，这些结果揭示了肿瘤免疫逃逸的替代机制，并支持针对衰老样中性粒细胞的免疫senolytics的开发，用于癌症治疗。
据介绍，肿瘤细胞促进免疫抑制性中性粒细胞的募集，中性粒细胞是骨髓细胞的一个亚群，驱动免疫抑制、肿瘤增殖和治疗耐药性。在生理学上，已知中性粒细胞的半衰期很短。
附：英文原文
Title: Apolipoprotein E induces pathogenic senescent-like myeloid cells in prostate cancer
Author: Nicolò Bancaro, Bianca Calì, Martina Troiani, Angela Rita Elia, Rydell Alvarez Arzola, Giuseppe Attanasio, Ping Lai, Mateus Crespo, Bora Gurel, Rita Pereira, Christina Guo, Simone Mosole, Daniela Brina, Mariantonietta D’Ambrosio, Emiliano Pasquini, Clarissa Spataro, Elena Zagato, Andrea Rinaldi, Mattia Pedotti, Simona Di Lascio, Francesco Meani, Monica Montopoli, Matteo Ferrari, Andrea Gallina, Luca Varani, Ricardo Pereira Mestre, Marco Bolis, Silke Gillessen Sommer, Johann de Bono, Arianna Calcinotto, Andrea Alimonti
Issue&Volume: 2023-03-02
Abstract: Tumor cells promote the recruitment of immunosuppressive neutrophils, a subset ofmyeloid cells driving immune suppression, tumor proliferation, and treatment resistance.Physiologically, neutrophils are known to have a short half-life. Here, we reportthe identification of a subset of neutrophils that have upregulated expression ofcellular senescence markers and persist in the tumor microenvironment. Senescent-likeneutrophils express the triggering receptor expressed on myeloid cells 2 (TREM2) andare more immunosuppressive and tumor-promoting than canonical immunosuppressive neutrophils.Genetic and pharmacological elimination of senescent-like neutrophils decreases tumorprogression in different mouse models of prostate cancer. Mechanistically, we havefound that apolipoprotein E (APOE) secreted by prostate tumor cells binds TREM2 onneutrophils, promoting their senescence. APOE and TREM2 expression increases in prostatecancers and correlates with poor prognosis. Collectively, these results reveal analternative mechanism of tumor immune evasion and support the development of immunesenolytics targeting senescent-like neutrophils for cancer therapy.
DOI: 10.1016/j.ccell.2023.02.004
Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00032-6
Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
官方网址：https://www.cell.com/cancer-cell/home
投稿链接：https://www.editorialmanager.com/cancer-cell/default.aspx
本期文章：《癌细胞》：Online/在线发表
