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Tim-4+腔内巨噬细胞损害抗肿瘤CD8+T细胞免疫
作者:小柯机器人 发布时间:2021/6/13 22:24:49

美国纪念斯隆-凯特琳癌症中心Taha Merghoub、Charles M. Rudin等研究人员合作发现,Tim-4+腔内巨噬细胞损害抗肿瘤CD8+T细胞免疫。相关论文于2021年6月10日在线发表在《癌细胞》杂志上。

研究人员表明,胸膜腔和腹腔的转移性疾病与免疫检查点阻断(ICB)治疗后的不良临床结果相关。腔内巨噬细胞表达高水平的Tim-4,一种磷脂酰丝氨酸(PS)受体,这与癌症患者胸腔积液和腹腔腹水中具有肿瘤反应特征的CD8+T细胞数量减少有关。

研究人员从机制上证明,细胞毒性的抗肿瘤CD8+T细胞上调PS,这使它们隔离于肿瘤靶标和并对Tim-4+巨噬细胞介导的增殖抑制敏感。Tim-4阻断消除了这种隔离和增殖抑制,并增强了小鼠抗PD-1治疗和过继性T细胞治疗模型中的抗肿瘤功效。因此,Tim-4+腔内巨噬细胞限制了免疫疗法在这些微环境中的功效。

据介绍,ICB已成为癌症的一项显著临床进展。然而,大多数患者对ICB治疗没有反应。

附:英文原文

Title: Tim-4+ cavity-resident macrophages impair anti-tumor CD8+ T cell immunity

Author: Andrew Chow, Sara Schad, Michael D. Green, Matthew D. Hellmann, Viola Allaj, Nicholas Ceglia, Giulia Zago, Nisargbhai S. Shah, Sai Kiran Sharma, Marissa Mattar, Joseph Chan, Hira Rizvi, Hong Zhong, Cailian Liu, Yonina Bykov, Dmitriy Zamarin, Hongyu Shi, Sadna Budhu, Corrin Wohlhieter, Fathema Uddin, Aditi Gupta, Inna Khodos, Jessica J. Waninger, Angel Qin, Geoffrey J. Markowitz, Vivek Mittal, Vinod Balachandran, Jennifer N. Durham, Dung T. Le, Weiping Zou, Sohrab P. Shah, Andrew McPherson, Katherine Panageas, Jason S. Lewis, Justin S.A. Perry, Elisa de Stanchina, Triparna Sen, John T. Poirier, Jedd D. Wolchok, Charles M. Rudin, Taha Merghoub

Issue&Volume: 2021-06-10

Abstract: Immune checkpoint blockade (ICB) has been a remarkable clinical advance for cancer;however, the majority of patients do not respond to ICB therapy. We show that metastaticdisease in the pleural and peritoneal cavities is associated with poor clinical outcomesafter ICB therapy. Cavity-resident macrophages express high levels of Tim-4, a receptorfor phosphatidylserine (PS), and this is associated with reduced numbers of CD8+ T cells with tumor-reactive features in pleural effusions and peritoneal ascitesfrom patients with cancer. We mechanistically demonstrate that viable and cytotoxicanti-tumor CD8+ T cells upregulate PS and this renders them susceptible to sequestration away fromtumor targets and proliferation suppression by Tim-4+ macrophages. Tim-4 blockade abrogates this sequestration and proliferation suppressionand enhances anti-tumor efficacy in models of anti-PD-1 therapy and adoptive T celltherapy in mice. Thus, Tim-4+ cavity-resident macrophages limit the efficacy of immunotherapies in these microenvironments.

DOI: 10.1016/j.ccell.2021.05.006

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00272-5

期刊信息

Cancer Cell:《癌细胞》,创刊于2002年。隶属于细胞出版社,最新IF:23.916
官方网址:https://www.cell.com/cancer-cell/home
投稿链接:https://www.editorialmanager.com/cancer-cell/default.aspx