Single-cell and spatial analysis reveal interaction of FAP+ fibroblasts and SPP1+ macrophages in colorectal cancer

• DOI: 10.1038/s41467-022-29366-6
• Publication Date: 2022-04-01T10:21:23Z
• Authors: Jingjing Qi; Hongxiang Sun; Yao Zhang; Zhengting Wang; Zhenzhen Xun; Ziyi Li; Xinyu Ding; Rujuan Bao; Liwen Hong; Wenqing Jia; Fei Fang; Hongzhi Liu; Lei Chen; Jie Zhong; Duowu Zou; Lianxin Liu; Leng Han; Florent Ginhoux; Yingbin Liu; Youqiong Ye; Bing Su
• Keywords: Cancer-Associated Fibroblasts

Abstract Colorectal cancer (CRC) is among the most common malignancies with limited treatments other than surgery. The tumor microenvironment (TME) profiling enables discovery of potential therapeutic targets. Here, we profile 54,103 cells from and adjacent tissues to characterize cellular composition elucidate origin regulation tumor-enriched cell types in CRC. We demonstrate that tumor-specific FAP + fibroblasts SPP1 macrophages were positively correlated 14 independent CRC cohorts containing 2550 samples validate their close localization by immuno-fluorescent staining spatial transcriptomics. This interaction might be regulated chemerin, TGF-β, interleukin-1, which would stimulate formation immune-excluded desmoplasic structure limit T infiltration. Furthermore, find patients high or expression achieved less benefit an anti-PD-L1 therapy cohort. Our results provide a strategy disrupting improve immunotherapy.