Single-cell transcriptome profiling of post-treatment and treatment-naïve colorectal cancer: Insights into putative mechanisms of chemoresistance
Abstract
Drug resistance remains a major clinical challenge in the treatment of colorectal cancer (CRC) with conventional chemotherapy regimens. Analyzing post-treatment changes in tumor cells and the tumor microenvironment (TME) is essential to understanding resistance development. We analyzed single-cell RNA sequencing (scRNAseq) data derived from 50 colorectal cancers (CRCs). This cohort included 30 treatment-naïve tumors (25 microsatellite stable (MSS) and five microsatellite unstable (MSI)) and 20 tumors that had previously received standard chemotherapy (comprising 14 responders and 6 progressors). Compared to MSS tumors, MSI tumors exhibited an immune-enriched tumor microenvironment (TME), marked by higher cytotoxic T cell activity and a less pronounced mesenchymal phenotype. Primary left-sided CRCs were associated with metastatic potential and depleted B cells. In post-treatment CRC, responders showed a high prevalence of a dendritic cell (DC) TME signature, which correlated with better survival in TCGA. Progressors showed TME enrichment of pericyte-like fibroblasts (associated with poor survival) and elevated exhausted CD8 T cells, suggesting a pro-inflammatory TME. Progressor tumor cells also expressed two chemo-protective markers, MTRNR2L1 and CDX1, coexpressed with the stemness-related immune-checkpoint CD24. In summary, scRNA-seq reveals distinct prognostic markers and features underlying progression to chemotherapy in MSS CRC.
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BibTeX
@article{puzanov2026singlecell,
title = {{Single-cell transcriptome profiling of post-treatment and treatment-naïve colorectal cancer: Insights into putative mechanisms of chemoresistance}},
author = {Grigory Puzanov and Clémence Astier and Dimitris Papakonstantinou and Mariana Quiroga Londoño and Camille Blériot and Andrey Yurchenko and Mohamed Amine Bani and Gérôme Jules-Clement and Fabrice Andre and Aurélien Marabelle and Antoine Hollebecque and Sergey Nikolaev},
journal = {Cancer Letters},
year = {2026},
month = sep,
doi = {10.1016/j.canlet.2025.218127},
url = {https://hal.science/hal-05762936v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Single-cell transcriptome profiling of post-treatment and treatment-naïve colorectal cancer: Insights into putative mechanisms of chemoresistance
AU - Grigory Puzanov
AU - Clémence Astier
AU - Dimitris Papakonstantinou
AU - Mariana Quiroga Londoño
AU - Camille Blériot
AU - Andrey Yurchenko
AU - Mohamed Amine Bani
AU - Gérôme Jules-Clement
AU - Fabrice Andre
AU - Aurélien Marabelle
AU - Antoine Hollebecque
AU - Sergey Nikolaev
PY - 2026
DA - 2026/09/24
JO - Cancer Letters
DO - 10.1016/j.canlet.2025.218127
UR - https://hal.science/hal-05762936v1
AB - Drug resistance remains a major clinical challenge in the treatment of colorectal cancer (CRC) with conventional chemotherapy regimens. Analyzing post-treatment changes in tumor cells and the tumor microenvironment (TME) is essential to understanding resistance development. We analyzed single-cell RNA sequencing (scRNAseq) data derived from 50 colorectal cancers (CRCs). This cohort included 30 treatment-naïve tumors (25 microsatellite stable (MSS) and five microsatellite unstable (MSI)) and 20 tumors that had previously received standard chemotherapy (comprising 14 responders and 6 progressors). Compared to MSS tumors, MSI tumors exhibited an immune-enriched tumor microenvironment (TME), marked by higher cytotoxic T cell activity and a less pronounced mesenchymal phenotype. Primary left-sided CRCs were associated with metastatic potential and depleted B cells. In post-treatment CRC, responders showed a high prevalence of a dendritic cell (DC) TME signature, which correlated with better survival in TCGA. Progressors showed TME enrichment of pericyte-like fibroblasts (associated with poor survival) and elevated exhausted CD8 T cells, suggesting a pro-inflammatory TME. Progressor tumor cells also expressed two chemo-protective markers, MTRNR2L1 and CDX1, coexpressed with the stemness-related immune-checkpoint CD24. In summary, scRNA-seq reveals distinct prognostic markers and features underlying progression to chemotherapy in MSS CRC.
SN - 0304-3835
ER -