JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

Accepted manuscript available online (unedited version)

Single-cell and spatial transcriptomic analysis reveals that an immune cell-related signature could predict clinical outcomes for microsatellite stable colorectal cancer patients receiving immunotherapy

Author(s): Shijin YUAN, Yan XIA, Guangwei DAI, Shun RAO, Rongrong HU, Yuzhen GAO, Qing QIU, Chenghao WU, Sai QIAO, Yinghua XU, Xinyou XIE, Haizhou LOU, Xian WANG, Jun ZHANG
Affiliation(s): Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, 310016, Zhejiang, China; more
Corresponding email(s): jameszhang2000@zju.edu.cn, wangx118@zju.edu.cn
Key Words: Colorectal cancer; Microsatellite stable; Immunotherapy; Single-cell RNA sequencing; Spatial transcriptomics

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Shijin YUAN, Yan XIA, Guangwei DAI, Shun RAO, Rongrong HU, Yuzhen GAO, Qing QIU, Chenghao WU, Sai QIAO, Yinghua XU, Xinyou XIE, Haizhou LOU, Xian WANG, Jun ZHANG. Single-cell and spatial transcriptomic analysis reveals that an immune cell-related signature could predict clinical outcomes for microsatellite stable colorectal cancer patients receiving immunotherapy[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2300679

@article{title="Single-cell and spatial transcriptomic analysis reveals that an immune cell-related signature could predict clinical outcomes for microsatellite stable colorectal cancer patients receiving immunotherapy",
author="Shijin YUAN, Yan XIA, Guangwei DAI, Shun RAO, Rongrong HU, Yuzhen GAO, Qing QIU, Chenghao WU, Sai QIAO, Yinghua XU, Xinyou XIE, Haizhou LOU, Xian WANG, Jun ZHANG",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B2300679"
}

%0 Journal Article
%T Single-cell and spatial transcriptomic analysis reveals that an immune cell-related signature could predict clinical outcomes for microsatellite stable colorectal cancer patients receiving immunotherapy
%A Shijin YUAN
%A Yan XIA
%A Guangwei DAI
%A Shun RAO
%A Rongrong HU
%A Yuzhen GAO
%A Qing QIU
%A Chenghao WU
%A Sai QIAO
%A Yinghua XU
%A Xinyou XIE
%A Haizhou LOU
%A Xian WANG
%A Jun ZHANG
%J Journal of Zhejiang University SCIENCE B
%P
%@ 1673-1581
%D in press
%I Zhejiang University Press & Springer
doi="https://doi.org/10.1631/jzus.B2300679"

TY - JOUR
T1 - Single-cell and spatial transcriptomic analysis reveals that an immune cell-related signature could predict clinical outcomes for microsatellite stable colorectal cancer patients receiving immunotherapy
A1 - Shijin YUAN
A1 - Yan XIA
A1 - Guangwei DAI
A1 - Shun RAO
A1 - Rongrong HU
A1 - Yuzhen GAO
A1 - Qing QIU
A1 - Chenghao WU
A1 - Sai QIAO
A1 - Yinghua XU
A1 - Xinyou XIE
A1 - Haizhou LOU
A1 - Xian WANG
A1 - Jun ZHANG
J0 - Journal of Zhejiang University Science B
SP -
EP -
%@ 1673-1581
Y1 - in press
PB - Zhejiang University Press & Springer
ER -
doi="https://doi.org/10.1631/jzus.B2300679"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: Recent data suggest that vascular endothelial growth factor receptor inhibitor (VEGFRi) could enhance the anti-tumor activity of the anti-PD-1 antibody in colorectal cancer (CRC) with microsatellite stability (MSS). However, the comparison between this combination and standard third-line VEGFRi treatment is not established and reliable biomarkers are still lacking. We retrospectively enrolled MSS CRC patients receiving anti-PD-1 antibody plus VEGFRi (combination group, n=54) or VEGFRi alone (VEGFRi group, n=32), and their efficacy and safety were evaluated. We additionally examined the immune characteristics of the MSS CRC tumor microenvironment (TME) through single-cell and spatial transcriptomic data, and an MSS CRC immune cell-related signature (MCICRS) predicting the clinical outcomes of MSS CRC patients receiving immunotherapy was developed and validated in our in-house cohort. Compared to VEGFRi alone, anti-PD-1 antibody and VEGFRi combination exhibited a prolonged survival benefit (median progression-free survival: 4.4 vs. 2.0 months, P=0.0024; median overall survival: 10.2 vs. 5.2 months, P=0.0038) and similar adverse events incidence. Through single-cell and spatial transcriptomic analyses, we determined 10 MSS CRC-enriched immune cell types and their spatial distribution, including naïve CD4T, regulatory CD4T, Th17, exhausted CD8T, cytotoxic CD8T, proliferated CD8T, NK, plasma, and classical and intermediated monocytes. Based on a systemic meta-analysis and 10 machine learning algorithms, we obtained MCICRS, an independent risk factor for the prognosis of MSS CRC patients. Further analyses demonstrated that the low-MCICRS group presented a higher immune cell infiltration and immune-related pathway activation, and hence a significant relation with the superior efficacy of pan-cancer immunotherapy. More importantly, the predictive value of MCICRS in MSS CRC receiving immunotherapy was also validated with the in-house cohort. Anti-PD-1 antibody combined with VEGFRi presented an improved clinical benefit in MSS CRC with manageable toxicity. MCICRS could serve as a robust and promising tool with which to predict clinical outcomes for individual MSS CRC patients receiving immunotherapy.

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