Single-cell and spatial analysis reveal interaction of FAP+ fibroblasts and SPP1+ macrophages in colorectal cancer.
IF: 17.694
Cited by: 114


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


Spatial Transcriptomics


Qi, Jingjing
Sun, Hongxiang
Zhang, Yao
Wang, Zhengting
Xun, Zhenzhen
Li, Ziyi
Ding, Xinyu
Bao, Rujuan
Hong, Liwen
Jia, Wenqing
Fang, Fei
Liu, Hongzhi
Chen, Lei
Zhong, Jie
Zou, Duowu
Liu, Lianxin
Han, Leng
Ginhoux, Florent
Liu, Yingbin
Ye, Youqiong
Su, Bing

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