美国斯坦福大学医学院Garry P. Nolan和Christian M. Schürch研究组取得一项新突破。他们发现在结肠直肠癌侵袭前相邻细胞间协调促进抗肿瘤免疫。这一研究成果于2020年8月6日在线发表在《细胞》上。

研究人员对石蜡包埋的组织微阵列重新利用CODEX蛋白组学分析平台进行分析，从而能够利用56种蛋白标记物同时分析35位晚期结直肠癌（CRC）患者的140个组织区域。研究人员确定了9个保守的、不同细胞邻域（CN），CN是CRC免疫肿瘤微环境（iTME）成分特征成的集合。仅富含PD-1⁺CD4⁺ T细胞的粒细胞CN与高危患者亚组中的生存率呈正相关。

肿瘤和免疫CNs的耦合、T细胞和巨噬细胞CNs的断裂以及CN间通讯的中断与不良预后相关。这项研究提供了探究如何通过细胞和空间域协同作用来进行复杂生物过程的新模型，例如抗肿瘤免疫。

据了解，抗肿瘤免疫需要iTME中各组分间系统的、空间细微的相互作用。理解有效和无效肿瘤控制过程中的这种协调行为将促进肿瘤免疫治疗。

附：英文原文

Title: Coordinated Cellular Neighborhoods Orchestrate Antitumoral Immunity at the Colorectal Cancer Invasive Front

Author: Christian M. Schürch, Salil S. Bhate, Graham L. Barlow, Darci J. Phillips, Luca Noti, Inti Zlobec, Pauline Chu, Sarah Black, Janos Demeter, David R. McIlwain, Nikolay Samusik, Yury Goltsev, Garry P. Nolan

Issue&Volume: 2020-08-06

Abstract: Antitumoral immunity requires organized, spatially nuanced interactions between components of the immune tumor microenvironment (iTME). Understanding this coordinated behavior in effective versus ineffective tumor control will advance immunotherapies. We re-engineered co-detection by indexing (CODEX) for paraffin-embedded tissue microarrays, enabling simultaneous profiling of 140 tissue regions from 35 advanced-stage colorectal cancer (CRC) patients with 56 protein markers. We identified nine conserved, distinct cellular neighborhoods (CNs)—a collection of components characteristic of the CRC iTME. Enrichment of PD-1+CD4+ T cells only within a granulocyte CN positively correlated with survival in a high-risk patient subset. Coupling of tumor and immune CNs, fragmentation of T cell and macrophage CNs, and disruption of inter-CN communication was associated with inferior outcomes. This study provides a framework for interrogating how complex biological processes, such as antitumoral immunity, occur through concerted actions of cells and spatial domains.

DOI: 10.1016/j.cell.2020.07.005

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30870-9