美国达纳-法伯癌症研究所Eliezer M. Van Allen团队揭示晚期肾细胞癌（RCC）免疫治疗期间的肿瘤和免疫重编程机制。该项研究成果发表在2021年3月11日出版的《癌细胞》杂志上。
他们表征了免疫检查点封锁（ICB）暴露之前或之后，来自转移性RCC患者的癌细胞和免疫细胞的单细胞转录组。在应答者中，细胞毒性T细胞的亚群表达更高水平的共抑制受体和效应分子。
响应于富含干扰素的微环境，来自处理过的活检组织的巨噬细胞向促炎状态转变，但同时也上调了免疫抑制标志物。在癌细胞中，他们将分支分为两个亚群，它们在血管生成信号传导和ICB后免疫抑制程序的上调方面不同。癌细胞亚群和免疫逃逸的表达特征与PBRM1突变以及原发性和ICB治疗的晚期RCC的生存有关。
他们的发现表明，ICB重塑了RCC微环境，并改变了癌症和免疫细胞群之间的相互作用，这对于理解ICB的反应和耐药性至关重要。
研究人员表示，ICB可在部分RCC患者中实现持久的疾病控制，但对耐药性驱动机制的了解却很少。
附：英文原文
Title: Tumor and immune reprogramming during immunotherapy in advanced renal cell carcinoma
Author: Kevin Bi, Meng Xiao He, Ziad Bakouny, Abhay Kanodia, Sara Napolitano, Jingyi Wu, Grace Grimaldi, David A. Braun, Michael S. Cuoco, Angie Mayorga, Laura DelloStritto, Gabrielle Bouchard, John Steinharter, Alok K. Tewari, Natalie I. Vokes, Erin Shannon, Maxine Sun, Jihye Park, Steven L. Chang, Bradley A. McGregor, Rizwan Haq, Thomas Denize, Sabina Signoretti, Jennifer L. Guerriero, Sébastien Vigneau, Orit Rozenblatt-Rosen, Asaf Rotem, Aviv Regev, Toni K. Choueiri, Eliezer M. Van Allen
Issue&Volume: 2021-03-11
Abstract: Immune checkpoint blockade (ICB) results in durable disease control in a subset of patients with advanced renal cell carcinoma (RCC), but mechanisms driving resistance are poorly understood. We characterize the single-cell transcriptomes of cancer and immune cells from metastatic RCC patients before or after ICB exposure. In responders, subsets of cytotoxic T cells express higher levels of co-inhibitory receptors and effector molecules. Macrophages from treated biopsies shift toward pro-inflammatory states in response to an interferon-rich microenvironment but also upregulate immunosuppressive markers. In cancer cells, we identify bifurcation into two subpopulations differing in angiogenic signaling and upregulation of immunosuppressive programs after ICB. Expression signatures for cancer cell subpopulations and immune evasion are associated with PBRM1 mutation and survival in primary and ICB-treated advanced RCC. Our findings demonstrate that ICB remodels the RCC microenvironment and modifies the interplay between cancer and immune cell populations critical for understanding response and resistance to ICB.
DOI: 10.1016/j.ccell.2021.02.015
Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00117-3
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
