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拮抗炎症表型决定肿瘤的命运和治疗反应
作者:小柯机器人 发布时间:2020/11/23 16:44:30

英国曼彻斯特大学Santiago Zelenay研究组发现,拮抗炎症表型决定肿瘤的命运以及对免疫检查点阻断的反应。该项研究成果于2020年11月20日在线发表在《免疫》杂志上。

通过深入研究与小鼠免疫依赖性控制相关的炎性肿瘤微环境(TME),研究人员寻找了癌症抑制性炎症的主要调节因子。研究人员发现,干扰素产生型自然杀伤(NK)细胞的早期肿瘤内积累诱导TME的重塑,并促进细胞毒T细胞(CTL)介导的肿瘤清除。

从机制上讲,肿瘤来源的前列腺素E2(PGE2)对NK细胞上的EP2和EP4受体有选择性地起作用,阻碍了TME的转换,并使免疫逃逸成为可能。对人类癌症患者数据集的分析显示,独特的炎症性TME表型类似于与小鼠的癌症免疫控制与逃避相关的炎症性TME表型。这使研究人员能够生成整合了相反炎症因子的基因表达特征,并预测患者的存活率和对免疫检查点阻断的反应。

这些发现确定了与癌症免疫控制相关的肿瘤炎症环境特征,并建立了预测免疫治疗结果的策略。

据悉,炎症可以促进或抑制癌症的进展以及对治疗的反应。

附:英文原文

Title: Antagonistic Inflammatory Phenotypes Dictate Tumor Fate and Response to Immune Checkpoint Blockade

Author: Eduardo Bonavita, Christian P. Bromley, Gustav Jonsson, Victoria S. Pelly, Sudhakar Sahoo, Katherine Walwyn-Brown, Sofia Mensurado, Agrin Moeini, Eimear Flanagan, Charlotte R. Bell, Shih-Chieh Chiang, C.P. Chikkanna-Gowda, Neil Rogers, Bruno Silva-Santos, Sebastien Jaillon, Alberto Mantovani, Caetano Reis e Sousa, Nadia Guerra, Daniel M. Davis, Santiago Zelenay

Issue&Volume: 2020-11-20

Abstract: Inflammation can support or restrain cancer progression and the response to therapy. Here, we searched for primary regulators of cancer-inhibitory inflammation through deep profiling of inflammatory tumor microenvironments (TMEs) linked to immune-dependent control in mice. We found that early intratumoral accumulation of interferon gamma (IFN-γ)-producing natural killer (NK) cells induced a profound remodeling of the TME and unleashed cytotoxic T cell (CTL)-mediated tumor eradication. Mechanistically, tumor-derived prostaglandin E2 (PGE2) acted selectively on EP2 and EP4 receptors on NK cells, hampered the TME switch, and enabled immune evasion. Analysis of patient datasets across human cancers revealed distinct inflammatory TME phenotypes resembling those associated with cancer immune control versus escape in mice. This allowed us to generate a gene-expression signature that integrated opposing inflammatory factors and predicted patient survival and response to immune checkpoint blockade. Our findings identify features of the tumor inflammatory milieu associated with immune control of cancer and establish a strategy to predict immunotherapy outcomes.

DOI: 10.1016/j.immuni.2020.10.020

Source: https://www.cell.com/immunity/fulltext/S1074-7613(20)30461-1

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新IF:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx