ArticleNature communications2022
Inflammation promotes resistance to immune checkpoint inhibitors in high microsatellite instability colorectal cancer.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 3 of them syntheses that pooled it.
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Who cites it
113 citing papers in PubMed, 3 syntheses or guidelines pooled it, 143 citations in OpenAlex.
- Prognostic value of the neutrophil-to-lymphocyte ratio in patients with colorectal cancer undergoing chemotherapy: a systematic review and meta-analysis.Frontiers in oncology · 2026Pooled it
- 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
- C-reactive protein (CRP) as a prognostic biomarker in patients with urothelial carcinoma: A systematic review and meta-analysis.Critical reviews in oncology/hematology · 2024Pooled it
- Nivolumab plus relatlimab in patients with previously treated microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: the phase II CheckMate 142 study.Journal for immunotherapy of cancer · 2024Trial
- Colorectal cancer landscape from gut microbiota: Insights into mutations, epigenetic dysregulation, and immune microenvironment alterations.Virulence · 2026Review
- PTPN22 as a novel therapeutic target: a key intracellular checkpoint for NK cell therapy.Journal for immunotherapy of cancer · 2026Article
- Systemic Inflammation and Risk of Thromboembolism, Mortality, and Treatment Response in Patients With Cancer Receiving Immune Checkpoint Inhibitors.European journal of clinical investigation · 2026Article
- IL-26-driven epigenetic remodeling promotes immune evasion in colorectal cancer.Nature communications · 2026Article
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- Harnessing the microbiome for cancer therapy.Nature reviews. Microbiology · 2026Review
- Inflammatory cytokines induce new cancer dependencies.Nature genetics · 2026Article
- Impact of lymph node dissection on survival outcomes in gastric cancer patients receiving immune checkpoint inhibitors.Medicine · 2026Article
- Nomogram-Based Prediction Model for Postherpetic Neuralgia in Immunosuppressive Patients.Journal of clinical medicine · 2026Article
- METTL3-mediated mJournal of translational medicine · 2026Article
- IL-11-IL6ST-STAT3 signaling defines a convergent inflammatory axis in esophageal cancer subtypes.Scientific reports · 2026Article
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- Dysregulated immune microenvironment in metastatic colorectal cancer.Medical oncology (Northwood, London, England) · 2026Article
- Methods and applications of patient-derived organoid models for immune microenvironment and immunotherapy research in multiple cancer types.Experimental hematology & oncology · 2026Review
- Prediction of immunotherapeutic responses by a classifier model based on inflammation-associated tumor microenvironment signatures in colorectal cancer.Discover oncology · 2026Article
- Cancer stem cell-driven drug resistance in colorectal carcinoma: molecular aspects and therapeutic potentials.Molecular cancer · 2026Review
53 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inflammation is a common medical complication in colorectal cancer (CRC) patients, which plays significant roles in tumor progression and immunosuppression. However, the influence of inflammatory conditions on the tumor response to immune checkpoint inhibitors (ICI) is incompletely understood. Here we show that in a patient with high microsatellite instability (MSI-H) CRC and a local inflammatory condition, the primary tumor progresses but its liver metastasis regresses upon Pembrolizumab treatment. In silico investigation prompted by this observation confirms correlation between inflammatory conditions and poor tumor response to PD-1 blockade in MSI-H CRCs, which is further validated in a cohort of 62 patients retrospectively enrolled to our study. Inhibition of local but not systemic immune response is verified in cultures of paired T cells and organoid cells from patients. Single-cell RNA sequencing suggests involvement of neutrophil leukocytes via CD80/CD86-CTLA4 signaling in the suppressive immune microenvironment. In concordance with this finding, elevated neutrophil-to-lymphocyte ratio indicates inhibited immune status and poor tumor response to ICIs. Receiver operating characteristic curve further demonstrates that both inflammatory conditions and a high NLR could predict a poor response to ICIs in MSI- CRCs, and the predictive value could be further increased when these two predictors are combined. Our study thus suggests that inflammatory conditions in MSI-H CRCs correlate with resistance to ICIs through neutrophil leukocyte associated immunosuppression and proposes both inflammatory conditions and high neutrophil-to-lymphocyte ratio as clinical features for poor ICI response.
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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.