ArticleProceedings of the National Academy of Sciences of the United States of America2021
Dendritic cell paucity in mismatch repair-proficient colorectal cancer liver metastases limits immune checkpoint blockade efficacy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 82 citations in OpenAlex.
- Evaluation of the Prognostic Role of Liver Metastases on Patient Outcomes: Systematic Review and Meta-analysis.Cancer journal (Sudbury, Mass.)Pooled it
- Early radiologic signal of responsiveness to immune checkpoint blockade in microsatellite-stable/mismatch repair-proficient metastatic colorectal cancer.British journal of cancer · 2022Trial
- [A transition from targeting immune evasion to a multidisciplinary collaborative treatment framework for "homotherapy for heteropathy" in liver metastases].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Fc-optimized GITR antibody enhances a CD4 T cell-dendritic cell crosstalk to promote antitumor immunity.Nature cancer · 2026Article
- Iron-Tannic Acid Hydrogel Mediated Mild Photothermal Therapy Combined With Ferroptosis Enhances Anti-Tumor Immunity in Colorectal Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Intratumoral Regulatory T-cell Ablation Mediates Tumor Control Systemically without Autoimmunity.Cancer research · 2026Article
- Mitochondria-Targeting Iridium(III) Complexes Induce PANoptosis and Ferroptosis for Boosting Chemoimmunotherapy Against Immune-Desert Colorectal Cancer.Angewandte Chemie (International ed. in English) · 2026Article
- Microenvironment-Driven Reprogramming in Colorectal Cancer Liver Metastasis: Metabolic, Phenotypic, and Immune Adaptation.International journal of molecular sciences · 2026Review
- DYRK1A enhances antitumor immunity in type 1 conventional dendritic cells via mTORC1 activation.The Journal of clinical investigation · 2026Article
- Enhancing Immunotherapeutic Response in Colorectal Cancer with a Neuropilin 1-Targeting Tumor-Penetrating Peptide.Cancer research communications · 2026Article
- The Molecular Signature of Early-Onset Colorectal Cancer Liver Metastases: Distinct Biology and Clinical Challenges.International journal of molecular sciences · 2026Review
- NEK8 kinase-mediated lactate increase impairs antitumor immunity decreasing radiotherapy sensitivity in colorectal cancer.Nature communications · 2026Article
- Research progress on immune tolerance mechanisms in liver metastatic tumors and the "Liver-metastasis-oriented shared-mechanism therapeutic strategy" approach.Medical review (2021) · 2026Review
- SPP1 Drives Colorectal Cancer Liver Metastasis and Immunotherapy Resistance by Stimulating CXCL12 Production in Cancer-Associated Fibroblasts.Cancer research · 2026Article
- Traditional Chinese medicine remodels the immune microenvironment of colorectal cancer: mechanisms and therapeutic perspectives.Frontiers in immunology · 2026Review
- Multipathway pharmacological interventions targeting liver-derived immune resistance in colorectal cancer liver metastasis.Frontiers in immunology · 2026Review
- Organ-specific pre-metastatic and metastatic niches in colorectal cancer: "discrepancy in response to immune checkpoint inhibitors in liver and lung metastasis".Frontiers in immunology · 2026Review
- Liver microenvironment-driven immunosuppressive niche in colorectal cancer liver metastasis and its therapeutic remodeling.Frontiers in immunology · 2026Review
- Beyond mismatch repair in colorectal cancer liver metastases: rethinking immunotherapy through the hepatic metastatic niche.Frontiers in immunology · 2026Article
- Spatial patterns and prognostic relevance of CD1aCancer immunology, immunotherapy : CII · 2025Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 2 institutions in 2 countries.
Funding
Abstract
Liver metastasis is a major cause of mortality for patients with colorectal cancer (CRC). Mismatch repair-proficient (pMMR) CRCs make up about 95% of metastatic CRCs, and are unresponsive to immune checkpoint blockade (ICB) therapy. Here we show that mouse models of orthotopic pMMR CRC liver metastasis accurately recapitulate the inefficacy of ICB therapy in patients, whereas the same pMMR CRC tumors are sensitive to ICB therapy when grown subcutaneously. To reveal local, nonmalignant components that determine CRC sensitivity to treatment, we compared the microenvironments of pMMR CRC cells grown as liver metastases and subcutaneous tumors. We found a paucity of both activated T cells and dendritic cells in ICB-treated orthotopic liver metastases, when compared with their subcutaneous tumor counterparts. Furthermore, treatment with Feline McDonough sarcoma (FMS)-like tyrosine kinase 3 ligand (Flt3L) plus ICB therapy increased dendritic cell infiltration into pMMR CRC liver metastases and improved mouse survival. Lastly, we show that human CRC liver metastases and microsatellite stable (MSS) primary CRC have a similar paucity of T cells and dendritic cells. These studies indicate that orthotopic tumor models, but not subcutaneous models, should be used to guide human clinical trials. Our findings also posit dendritic cells as antitumor components that can increase the efficacy of immunotherapies against pMMR CRC.
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Registered trials
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.