The single-cell spatial landscape of stage III colorectal cancers

间质细胞 质量细胞仪 肿瘤微环境 表型 结直肠癌 细胞 免疫系统 生物 癌症研究 单细胞分析 微卫星不稳定性 淋巴细胞 病理 医学 癌症 免疫学 微卫星 遗传学 等位基因 基因
作者
Andrew Su,HoJoon Lee,Minh‐Phuong Tran,Richard Cruz,Anuja Sathe,Xiangqi Bai,Ignacio A. Wichmann,Lance Pflieger,Bryce Moulton,Tyler Barker,Derrick S. Haslem,David A. Jones,Lincoln Nadauld,Quan Nguyen,Hanlee P. Ji,Terence D. Rhodes
标识
DOI:10.1101/2024.11.07.622577
摘要

We conducted a spatial analysis using imaging mass cytometry applied to stage III colorectal adenocarcinomas. This study used multiplexed markers to distinguish individual cells and their spatial organization from 52 colorectal cancers. We determined the landscape features of cellular spatial features in the CRC tumor microenvironment. This spatial single-cell analysis identified 10 unique cell phenotypes in the tumor microenvironment that included stromal and immune cells with a subset which had a proliferative phenotype. These special features included spatial neighborhood interactions between single cells as well as different tissue niches, especially the tumor infiltrating lymphocyte regions. We applied a robust statistical analysis to identify significant correlations of cell features with phenotypes such as microsatellite instability or recurrence. We determined that microsatellite stable (MSS) colorectal cancers had an increased risk of recurrence if they had the following features: 1) a low level of stromal tumor-infiltrating lymphocytes, and 2) low interactions between CD4+ T cells and stromal cells. Our results point to the utility of spatial single-cell interaction analysis in defining novel features of the tumor immune microenvironments and providing useful clinical cell-related spatial biomarkers.
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