ArticleBMC medicine2023
Single-cell sequencing reveals the immune microenvironment landscape related to anti-PD-1 resistance in metastatic colorectal cancer with high microsatellite instability.
Article in BMC medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 2 of them syntheses that pooled it.
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Who cites it
43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 42 citations in OpenAlex.
- A Comprehensive Evaluation of the Effectiveness and Safety of Pembrolizumab for the Treatment of Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis.Current cancer drug targets · 2026Pooled it
- Neoadjuvant Immune Checkpoint Inhibition in MSI-H/dMMR Colorectal Cancer: A Systematic Review of Prospective Trials Evaluating Efficacy, Pathologic Response, and Surgical Outcomes.Journal of gastrointestinal cancer · 2025Pooled it
- Mechanisms and advances of drug resistance in colorectal cancer: A systematic overview of multi-layered regulatory networks.Translational oncology · 2026Review
- Review
- Research progress in diagnosis and treatment of pancreatic cancer with mismatch repair and microsatellite instability.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Establishing human immune system mice: application, opportunity, and challenges.Experimental & molecular medicine · 2026Review
- Long-Term Outcomes and Surgical Conversion After Immunotherapy in Microsatellite Instability-H Biliary Tract Cancers.JCO precision oncology · 2026Observational
- Lipid metabolism as a central driver of immune remodeling and therapeutic vulnerability in metastatic colorectal cancer.Lipids in health and disease · 2026Review
- Single-cell mapping of tumor-driven macrophage reprogramming via ETV4-MC1R underlies immunotherapy resistance in colorectal cancer.International journal of surgery (London, England) · 2026Article
- Intratumoral heterogeneity in microsatellite instability status at single-cell resolution.iScience · 2026Article
- Decoding Immunotherapy Response in Colorectal Cancer: Translational Insights Beyond MSI.Cancers · 2026Review
- Reshaping the colorectal cancer immune microenvironment: insights from single-cell and spatial omics.Cancer cell international · 2026Review
- Prediction of immunotherapeutic responses by a classifier model based on inflammation-associated tumor microenvironment signatures in colorectal cancer.Discover oncology · 2026Article
- Understanding the Tumor Microenvironmental Mechanisms Driving Immunotherapy Resistance in Colorectal Cancer Liver Metastases.Oncology research · 2026Review
- Myeloid-derived suppressor cells in colorectal cancer: mechanisms of immunosuppression, therapy resistance and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- Myeloid-derived suppressor cells and regulatory T cells in colorectal cancer: a synergistic immunosuppressive axis and emerging therapeutic opportunities.Frontiers in immunology · 2026Review
- Single-cell transcriptome analysis reveals regulatory programs associated with tumor resistance during immunotherapy in colorectal cancer.International journal of surgery (London, England) · 2026Article
- Synthetic lethality in cancer therapy: Mechanisms, models and clinical translation for overcoming therapeutic resistance.Clinical and translational medicine · 2026Review
- The application and prospect of granzyme B-targeted PET imaging in cancer immunotherapy.Journal of translational medicine · 2025Review
- SLC25A39 regulates Hedgehog signaling to promote tumor progression and sorafenib resistance in hepatocellular carcinoma.Scientific reports · 2025Article
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe objective response rate of microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) patients with first-line anti-programmed cell death protein-1 (PD-1) monotherapy is only 40-45%. Single-cell RNA sequencing (scRNA-seq) enables unbiased analysis of the full variety of cells comprising the tumor microenvironment. Thus, we used scRNA-seq to assess differences among microenvironment components between therapy-resistant and therapy-sensitive groups in MSI-H/mismatch repair-deficient (dMMR) mCRC. Resistance-related cell types and genes identified by this analysis were subsequently verified in clinical samples and mouse models to further reveal the molecular mechanism of anti-PD-1 resistance in MSI-H or dMMR mCRC.
methodsThe response of primary and metastatic lesions to first-line anti-PD-1 monotherapy was evaluated by radiology. Cells from primary lesions of patients with MSI-H/dMMR mCRC were analyzed using scRNA-seq. To identify the marker genes in each cluster, distinct cell clusters were identified and subjected to subcluster analysis. Then, a protein‒protein interaction network was constructed to identify key genes. Immunohistochemistry and immunofluorescence were applied to verify key genes and cell marker molecules in clinical samples. Immunohistochemistry, quantitative real-time PCR, and western blotting were performed to examine the expression of IL-1β and MMP9. Moreover, quantitative analysis and sorting of myeloid-derived suppressor cells (MDSCs) and CD8
resultsTumor responses in 23 patients with MSI-H/dMMR mCRC were evaluated by radiology. The objective response rate was 43.48%, and the disease control rate was 69.57%. ScRNA-seq analysis showed that, compared with the treatment-resistant group, the treatment-sensitive group accumulated more CD8
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.