Distinctive multicellular immunosuppressive hubs confer different intervention strategies for left-and right-sided colon cancers

Sep 21, 2026

Uploaded by Maeve

Primary colon cancers arising from the left and right sides show distinct clinical and molecular features shaped by oncogenic properties and multicellular tumor microenvironment interactions. By analyzing transcriptomic profiles from 426,863 single cells across 105 colon cancer patients and validating with spatial transcriptomics and large-scale histology, the study defines two side-specific expression meta-programs. The proliferation stemness program dominates left-sided malignant epithelia, forming a glucose metabolism reprogramming niche, while the immune secretory program enriches right-sided epithelia, especially in smoking patients. The IShigh state localizes to hypoxic regions, supporting immune evasion and different treatment responses.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages25

Reading Time1 h 3 min

AccessFree to download

Summary

Introduction

Key Methods and Evidence

Single-cell transcriptome integration

Spatial transcriptomics and histological validation

Findings and Side-Specific Meta-Programs

Proliferation stemness niche on left-sided tumors

Immune secretory program on right-sided tumors

Clinical and Treatment Implications

Article Distinctive multicellular immunosuppressive hubs confer different intervention strategies for left-and right-sided colon cancers Authors Bingxin Liu, Shuwei Li, Yifei Cheng, ..., Mulong Du, Zhengdong Zhang, Meilin Wang Correspondence [mwang@njmu.edu.cn](mwang@njmu.edu.cn) In brief Liu et al. reveal shared and distinct features of left-and right-sided colon cancers by integrating single-cell transcriptome, spatial transcriptome, and large-scale omics analysis. PShigh and IShigh malignant epithelia drive distinct immunosuppressive patterns in two tumor types, leading to varying clinical outcomes and treatment responses inpatients. d An scRNA-seq study reveals shared and distinct features of both sides of colon cancer d The PShigh malignant epithelia shape the glucose metabolism reprogramming niche d The IShigh malignant epithelia spatially localize in hypoxic regions d IS meta-program predicts clinical response to ICI therapy in RCC Liu et al., 2024, Cell Reports Medicine 5, 101589 June 18, 2024 ª 2024 The Author(s) . Published by Elsevier Inc. [https://doi.org/10.1016/j.xcrm.2024.101589](https://doi.org/10.1016/j.xcrm.2024.101589) ll ll OPEN ACCESS Article Distinctive multicellular immunosuppressive hubs confer different intervention strategies for left-and right-sided colon cancers Bingxin Liu,1,2,7 Shuwei Li,1,2,7 Yifei Cheng,1,2,7 Peng Song,1,3 Menghuan Xu,1,2 Zhengyi Li,1,2 Wei Shao,1,2 Junyi Xin,1,2 Zan Fu,4 Dongying Gu,5 Mulong Du,1,2 Zhengdong Zhang,1,2 and Meilin Wang1,2,6,8,* 1Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, China 2Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China 3Department of Gastroenterology, Nanjing Drum Tower Hospital, The Afﬁliated Hospital of Nanjing University Medical School, Nanjing, China 4Department of General Surgery, The First Afﬁliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, China 5Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China 6The Afﬁliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China 7These authors contributed equally 8Lead contact *[Correspondence:](Correspondence: mwang@njmu.edu.cn)[ mwang@njmu.edu.cn](Correspondence: mwang@njmu.edu.cn) [https://doi.org/10.1016/j.xcrm.2024.101589](https://doi.org/10.1016/j.xcrm.2024.101589) SUMMARY Primary colon cancers arising from the left and right sides exhibit distinct clinical and molecular characteristics. Sidedness-associated heterogeneity relies intricately on the oncogenic properties of cancer cells and multicellular interactions in tumor microenvironments. Here, combining transcriptomic proﬁling of 426,863 single cells from 105 colon cancer patients and validation with spatial transcriptomics and large-scale histological analysis, we capture common transcriptional heterogeneity patterns between left-and right-sided malignant epithelia through delineating two side-speciﬁc expression meta-programs. The proliferation stemness meta-program is notably enriched in left-sided malignant epithelia that colocalize with Mph-PLTP cells, activated regulatory T cells (Tregs), and exhausted CD8-LAYN cells, constituting the glucose metabolism reprogramming niche. The immune secretory (IS) meta-program exhibits speciﬁc enrichment in right-sided malignant epithelia, especially in smoking patients with right-sided colon cancer. The IShigh malignant epithelia spatially localize in hypoxic regions and facilitate immune evasion through attenuating MphSPP1 cell antigen presentation and recruiting innate-like cytotoxicity-reduc

FAQs

What is the main difference between left- and right-sided colon cancers in this study?

Left- and right-sided colon cancers display distinct clinical and molecular characteristics driven by heterogeneity across cancer cell states and tumor microenvironment interactions.

How were shared and distinct features between the two tumor sides identified?

The study integrates single-cell transcriptomic data, then validates results with spatial transcriptomics and large-scale histological analysis, defining two side-specific expression meta-programs.

What do the proliferation stemness and immune secretory meta-programs correspond to?

The proliferation stemness meta-program is enriched in left-sided malignant epithelia and forms a glucose metabolism reprogramming niche, while the immune secretory (IS) meta-program shows specific enrichment in right-sided malignant epithelia, particularly in smoking patients.

Sep 21, 2026

Uploaded by Maeve