小柯机器人

切换到桌面版
产生IL-5的CD4+T细胞和嗜酸性粒细胞合作来增强对乳腺癌免疫检查点阻断的反应
2022-12-18 17:08
来源：小柯机器人

荷兰癌症研究所Marleen Ko等研究人员合作发现，产生IL-5的CD4+T细胞和嗜酸性粒细胞合作来增强对乳腺癌免疫检查点阻断（ICB）的反应。相关论文于2022年12月15日在线发表在《癌细胞》杂志上。

研究人员将对接受ICB治疗的转移性乳腺癌患者的血液和肿瘤的无偏见分析，与乳腺癌小鼠模型的机制研究相结合。研究人员观察到患者和小鼠中对ICB治疗有反应的全身性和瘤内嗜酸性粒细胞的增加。从机制上讲，ICB增加了CD4+T细胞的IL-5产量，刺激了骨髓中嗜酸性粒细胞产量的升高，导致了全身性嗜酸性粒细胞的扩张。通过ICB-顺铂组合或重组IL-33的额外诱导，能够促进瘤内嗜酸细胞浸润和嗜酸细胞依赖的CD8+T细胞激活，以增强ICB反应。这项工作证明了嗜酸性粒细胞在ICB反应中的关键作用，并提供了嗜酸性粒细胞参与增强ICB疗效的原理性证明。
 
据介绍，ICB预示着癌症治疗的一个新时代。对ICB反应机制的研究主要集中在T细胞上；然而，有效的免疫反应需要先天性和适应性免疫细胞之间紧密调节的交流。
 
附：英文原文

Title: IL-5-producing CD4+ T cells and eosinophils cooperate to enhance response to immune checkpoint blockade in breast cancer

Author: Olga S. Blomberg, Lorenzo Spagnuolo, Hannah Garner, Leonie Voorwerk, Olga I. Isaeva, Ewald van Dyk, Noor Bakker, Myriam Chalabi, Chris Klaver, Maxime Duijst, Kelly Kersten, Marieke Brüggemann, Dorien Pastoors, Cheei-Sing Hau, Kim Vrijland, Elisabeth A.M. Raeven, Daphne Kaldenbach, Kevin Kos, Inna S. Afonina, Paulien Kaptein, Louisa Hoes, Willemijn S.M.E. Theelen, Paul Baas, Emile E. Voest, Rudi Beyaert, Daniela S. Thommen, Lodewyk F.A. Wessels, Karin E. de Visser, Marleen Kok

Issue&Volume: 2022-12-15

Abstract: Immune checkpoint blockade (ICB) has heralded a new era in cancer therapy. Research into the mechanisms underlying response to ICB has predominantly focused on T cells; however, effective immune responses require tightly regulated crosstalk between innate and adaptive immune cells. Here, we combine unbiased analysis of blood and tumors from metastatic breast cancer patients treated with ICB with mechanistic studies in mouse models of breast cancer. We observe an increase in systemic and intratumoral eosinophils in patients and mice responding to ICB treatment. Mechanistically, ICB increased IL-5 production by CD4+ T cells, stimulating elevated eosinophil production from the bone marrow, leading to systemic eosinophil expansion. Additional induction of IL-33 by ICB-cisplatin combination or recombinant IL-33 promotes intratumoral eosinophil infiltration and eosinophil-dependent CD8+ T cell activation to enhance ICB response. This work demonstrates the critical role of eosinophils in ICB response and provides proof-of-principle for eosinophil engagement to enhance ICB efficacy.

DOI: 10.1016/j.ccell.2022.11.014

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00561-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


本期文章：《癌细胞》：Online/在线发表

分享到:

0