ArticleCancer immunology, immunotherapy : CII2015
Liver myeloid-derived suppressor cells expand in response to liver metastases in mice and inhibit the anti-tumor efficacy of anti-CEA CAR-T.
Article in Cancer immunology, immunotherapy : CII, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 144 papers, 1 of them a synthesis that pooled it.
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The trial behind it
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
144 citing papers in PubMed, 1 synthesis or guideline pooled it, 220 citations in OpenAlex.
- Systematic review of the use of granulocyte-macrophage colony-stimulating factor in patients with advanced melanoma.Cancer immunology, immunotherapy : CII · 2016Pooled it
- Leveraging Microphysiological Systems to Facilitate Neutrophil-Based Cancer Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- GM-CSF Promotes Neutrophil PD-L1 Expression Through the VEGFR-2/STAT6/CSF2 Signaling Axis in Oral Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Determinants of Chimeric Antigen Receptor (CAR) T Cell Success: In Vitro and In Vivo Preclinical Assessment.Cancers · 2026Review
- Ibrutinib and PD-1 Blockade Potentiate Mesothelin-Targeting CAR T-cell Therapy in Preclinical Models of Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Optimization of a parallel CAR for B-cell lymphoma via ITAM attenuation and target specificity validation.Clinical and experimental immunology · 2026Article
- Understanding the Tumor Microenvironmental Mechanisms Driving Immunotherapy Resistance in Colorectal Cancer Liver Metastases.Oncology research · 2026Review
- Gut Microbiota-Immune Interactions in Endometrial Cancer: Causal Mediation and Subtype-Specific Mechanisms.International journal of women's health · 2026Article
- Immune Checkpoint Blockade and Emerging Combination Platforms in Breast Cancer: A Narrative Review.Breast cancer (Dove Medical Press) · 2026Review
- Resistance mechanisms and overcoming strategies for CAR T-cell therapy in B-cell hematologic malignancies.Frontiers in immunology · 2026Review
- Review
- Transforming cancer immunotherapy: integration of distinct immune-based approaches as redefined dual immunotherapy with potential third-sensitizer.Experimental hematology & oncology · 2025Review
- Pitfalls and strategies of CAR-T therapy in solid tumors and implications for chordoma treatment.Immunotherapy · 2025Review
- Role of cell-based therapies in digestive disorders: Obstacles and opportunities.Regenerative therapy · 2025Review
- Review
- The Bidirectional Interplay between T Cell-Based Immunotherapies and the Tumor Microenvironment.Cancer immunology research · 2025Review
- Recent advancements in improving the efficacy and safety of chimeric antigen receptor (CAR)-T cell therapy for hepatocellular carcinoma.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- A Comprehensive Review on Novel Therapies for Gastrointestinal Cancers using Translational Platforms.Current pharmaceutical design · 2025Review
- Smart CAR-T Nanosymbionts: archetypes and proto-models.Frontiers in immunology · 2025Review
84 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 6 institutions in 1 country.
Funding
Abstract
Chimeric antigen receptor-modified T cell (CAR-T) technology, a promising immunotherapeutic tool, has not been applied specifically to treat liver metastases (LM). While CAR-T delivery to LM can be optimized by regional intrahepatic infusion, we propose that liver CD11b+Gr-1+ myeloid-derived suppressor cells (L-MDSC) will inhibit the efficacy of CAR-T in the intrahepatic space. We studied anti-CEA CAR-T in a murine model of CEA+ LM and identified mechanisms through which L-MDSC expand and inhibit CAR-T function. We established CEA+ LM in mice and studied purified L-MDSC and responses to treatment with intrahepatic anti-CEA CAR-T infusions. L-MDSC expanded threefold in response to LM, and their expansion was dependent on GM-CSF, which was produced by tumor cells. L-MDSC utilized PD-L1 to suppress anti-tumor responses through engagement of PD-1 on CAR-T. GM-CSF, in cooperation with STAT3, promoted L-MDSC PD-L1 expression. CAR-T efficacy was rescued when mice received CAR-T in combination with MDSC depletion, GM-CSF neutralization to prevent MDSC expansion, or PD-L1 blockade. As L-MDSC suppressed anti-CEA CAR-T, infusion of anti-CEA CAR-T in tandem with agents targeting L-MDSC is a rational strategy for future clinical trials.
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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.