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

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 () and Bing Su ()
Additional contact information
Jingjing Qi: Shanghai Jiao Tong University School of Medicine
Hongxiang Sun: Shanghai Jiao Tong University School of Medicine
Yao Zhang: Shanghai Jiao Tong University School of Medicine
Zhengting Wang: Shanghai Jiao Tong University School of Medicine
Zhenzhen Xun: Shanghai Jiao Tong University School of Medicine
Ziyi Li: Shanghai Jiao Tong University School of Medicine
Xinyu Ding: Shanghai Jiao Tong University School of Medicine
Rujuan Bao: Shanghai Jiao Tong University School of Medicine
Liwen Hong: Shanghai Jiao Tong University School of Medicine
Wenqing Jia: Shanghai Jiao Tong University School of Medicine
Fei Fang: Shanghai Jiao Tong University School of Medicine
Hongzhi Liu: Shanghai Jiao Tong University School of Medicine
Lei Chen: Shanghai Jiao Tong University School of Medicine
Jie Zhong: Shanghai Jiao Tong University School of Medicine
Duowu Zou: Shanghai Jiao Tong University School of Medicine
Lianxin Liu: University of Science and Technology of China
Leng Han: The University of Texas Health Science Center at Houston McGovern Medical School
Florent Ginhoux: Shanghai Jiao Tong University School of Medicine
Yingbin Liu: Shanghai Jiao Tong University School of Medicine
Youqiong Ye: Shanghai Jiao Tong University School of Medicine
Bing Su: Shanghai Jiao Tong University School of Medicine

Nature Communications, 2022, vol. 13, issue 1, 1-20

Abstract: Abstract 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29366-6

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DOI: 10.1038/s41467-022-29366-6

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