小柯机器人

美国梅奥诊所生物化学与分子生物学系Darren J. Baker研究组发现了衰老肺泡巨噬细胞促进早期肺肿瘤发生。相关论文于2023年6月1日发表在《癌细胞》杂志上。

在一个致癌Kras驱动的肺癌小鼠模型中，他们发现衰老细胞，特别是肺泡巨噬细胞，在肿瘤形成的早期积累。这些巨噬细胞上调p16INK4a和Cxcr1的表达，不同于先前定义的亚群，对衰老干预敏感，并抑制细胞毒性T细胞反应。它们的去除可以减轻小鼠腺瘤的发展和进展，表明它们促进肿瘤发生的作用。重要的是，他们发现具有这些特性的肺泡巨噬细胞在小鼠肺和人肺原位腺癌中随着正常衰老而增加。

总的来说，他们的研究表明，组织内巨噬细胞的一个亚群可以通过改变其局部微环境来支持肿瘤转化，这表明针对衰老巨噬细胞的治疗干预可能会在疾病的早期阶段减缓肺癌的进展。

据介绍，衰老细胞在肿瘤发生过程中发挥相关但依赖于环境的作用。

附：英文原文

Title: Senescent alveolar macrophages promote early-stage lung tumorigenesis

Author: Luis I. Prieto, Ines Sturmlechner, Sara I. Graves, Cheng Zhang, Nick P. Goplen, Eunhee S. Yi, Jie Sun, Hu Li, Darren J. Baker

Issue&Volume: 2023-06-01

Abstract: Senescent cells play relevant but context-dependent roles during tumorigenesis. Here,in an oncogenic Kras-driven lung cancer mouse model, we found that senescent cells, specifically alveolarmacrophages, accumulate early in neoplasia. These macrophages have upregulated expressionof p16INK4a and Cxcr1, are distinct from previously defined subsets and are sensitive to senolytic interventions,and suppress cytotoxic T cell responses. Their removal attenuates adenoma developmentand progression in mice, indicating their tumorigenesis-promoting role. Importantly,we found that alveolar macrophages with these properties increase with normal agingin mouse lung and in human lung adenocarcinoma in situ. Collectively, our study indicates that a subset of tissue-resident macrophages cansupport neoplastic transformation through altering their local microenvironment, suggestingthat therapeutic interventions targeting senescent macrophages may attenuate lungcancer progression during early stages of disease.

DOI: 10.1016/j.ccell.2023.05.006

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00171-X

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