Single-Cell and Spatial Analysis Reveal the Differences Between Left-Sided and Right-Sided Colorectal Cancer.

Authors

Zongnai Zhang, Jiaqi Xu, Yingchao Wu, Tao Liu, Junling Zhang, Mai Zhou, Jie Qiao, Heng Pan, Xin Wang

Published in

Cell proliferation. Pages e70260. Jul 14, 2026. Epub Jul 14, 2026.

Abstract

Colorectal cancer (CRC) exhibits heterogeneity based on tumour laterality, with right-sided tumours demonstrating distinct genetic, immunogenic and clinical behaviours compared to left-sided counterparts. In this study, we conducted single-cell RNA sequencing and spatial transcriptomics to dissect the distinct molecular landscapes of left- and right-sided CRC. We identified enhanced germinal centre B cell infiltration and CXCL13⁺ T cell enrichment, features linked to adaptive immune priming and better immunotherapy responsiveness. Right-sided CRC epithelial cells exhibited proliferative and immunogenic phenotypes, marked by upregulated immune-related pathways and chemokine-driven interactions with lymphocytes. Spatial analysis revealed organized tertiary lymphoid structure-immune microenvironment crosstalk in right-sided tumours, mediated by CCL19/21-CCR7 signalling. In contrast, left-sided CRC tumours displayed stromal-epithelial interactions favouring angiogenesis and metabolic reprogramming. Our findings established a laterality-specific immune microenvironment in CRC, providing insights for precise therapeutic strategies of left- and right-sided CRC.

PMID:
42444407
Bibliographic data and abstract were imported from PubMed on 14 Jul 2026.

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