美国加州大学Matthew H. Spitzer研究组近日取得一项新成果。他们提出肿瘤模型中免疫宏观环境的系统功能障碍和可塑性。相关论文发表在2020年5月25日出版的《自然—医学》杂志上。
在这项研究中，他们使用了流式细胞仪来定义系统免疫状况，以响应八个小鼠肿瘤模型中五个组织之间的肿瘤发展。系统性免疫力在不同模型和时间之间发生了巨大变化，在乳腺癌患者的外周血中发现了一致的结果。周围组织的变化不同于肿瘤微环境的变化。已经患过肿瘤的免疫系统的小鼠对正交攻击的反应减弱，包括在病毒或细菌感染过程中，减少的T细胞活化。
在这种情况下，抗原呈递细胞（APC）的反应较弱，而促进APC活化则挽救了T细胞活性。系统性免疫改变可通过外科手术切除而逆转，许多被白介素-1或粒细胞集落刺激因子阻滞所阻止，显示出系统性免疫状态下的显著可塑性。这些结果表明，肿瘤的发展动态地改变了免疫宏观环境的组成和功能。
附：英文原文
Title: Systemic dysfunction and plasticity of the immune macroenvironment in cancer models
Author: Breanna M. Allen, Kamir J. Hiam, Cassandra E. Burnett, Anthony Venida, Rachel DeBarge, Iliana Tenvooren, Diana M. Marquez, Nam Woo Cho, Yaron Carmi, Matthew H. Spitzer
Issue&Volume: 2020-05-25
Abstract: Understanding of the factors governing immune responses in cancer remains incomplete, limiting patient benefit. In this study, we used mass cytometry to define the systemic immune landscape in response to tumor development across five tissues in eight mouse tumor models. Systemic immunity was dramatically altered across models and time, with consistent findings in the peripheral blood of patients with breast cancer. Changes in peripheral tissues differed from those in the tumor microenvironment. Mice with tumor-experienced immune systems mounted dampened responses to orthogonal challenges, including reduced T cell activation during viral or bacterial infection. Antigen-presenting cells (APCs) mounted weaker responses in this context, whereas promoting APC activation rescued T cell activity. Systemic immune changes were reversed with surgical tumor resection, and many were prevented by interleukin-1 or granulocyte colony-stimulating factor blockade, revealing remarkable plasticity in the systemic immune state. These results demonstrate that tumor development dynamically reshapes the composition and function of the immune macroenvironment.
DOI: 10.1038/s41591-020-0892-6
Source: https://www.nature.com/articles/s41591-020-0892-6
Nature Medicine：《自然—医学》，创刊于1995年。隶属于施普林格·自然出版集团，最新IF：87.241
官方网址：https://www.nature.com/nm/
投稿链接：https://mts-nmed.nature.com/cgi-bin/main.plex
本期文章：《自然—医学》：Online/在线发表
