美国约翰霍普金斯大学医学院Arsen Osipov等研究人员合作完成抗PD-1疗法新辅助治疗后胰腺癌肿瘤微环境变化的多组学分析。这一研究成果于2022年10月27日在线发表在国际学术期刊《癌细胞》上。
Title: Multi-omic analyses of changes in the tumor microenvironment of pancreatic adenocarcinoma following neoadjuvant treatment with anti-PD-1 therapy
Author: Keyu Li, Joseph A. Tandurella, Jessica Gai, Qingfeng Zhu, Su Jin Lim, Dwayne L. Thomas, Tao Xia, Guanglan Mo, Jacob T. Mitchell, Janelle Montagne, Melissa Lyman, Ludmila V. Danilova, Jacquelyn W. Zimmerman, Benedict Kinny-Kster, Tengyi Zhang, Linda Chen, Alex B. Blair, Thatcher Heumann, Rose Parkinson, Jennifer N. Durham, Amol K. Narang, Robert A. Anders, Christopher L. Wolfgang, Daniel A. Laheru, Jin He, Arsen Osipov
Issue&Volume: 2022-10-27
Abstract: Successful pancreatic ductal adenocarcinoma (PDAC) immunotherapy necessitates optimization and maintenance of activated effector T cells (Teff). We prospectively collected and applied multi-omic analyses to paired pre- and post-treatment PDAC specimens collected in a platform neoadjuvant study of granulocyte-macrophage colony-stimulating factor-secreting allogeneic PDAC vaccine (GVAX) vaccine ± nivolumab (anti-programmed cell death protein 1 [PD-1]) to uncover sensitivity and resistance mechanisms. We show that GVAX-induced tertiary lymphoid aggregates become immune-regulatory sites in response to GVAX + nivolumab. Higher densities of tumor-associated neutrophils (TANs) following GVAX + nivolumab portend poorer overall survival (OS). Increased T cells expressing CD137 associated with cytotoxic Teff signatures and correlated with increased OS. Bulk and single-cell RNA sequencing found that nivolumab alters CD4+ T cell chemotaxis signaling in association with CD11b+ neutrophil degranulation, and CD8+ T cell expression of CD137 was required for optimal T cell activation. These findings provide insights into PD-1-regulated immune pathways in PDAC that should inform more effective therapeutic combinations that include TAN regulators and T cell activators.
DOI: 10.1016/j.ccell.2022.10.001
Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(22)00492-5
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