ArticleInternational journal of molecular sciences2024
Pexidartinib and Immune Checkpoint Inhibitors Combine to Activate Tumor Immunity in a Murine Colorectal Cancer Model by Depleting M2 Macrophages Differentiated by Cancer-Associated Fibroblasts.
Article in International journal of molecular sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Pathophysiological roles of monocytes and macrophages in cancer.Nature reviews. Immunology · 2026Review
- Anoikis in cancer: molecular mechanisms, resistance, and therapeutic strategies.Apoptosis : an international journal on programmed cell death · 2026Review
- Macrophage-Derived PDGF-BB and GDF-15 Promote Drug Resistance in KRAS-Mutant Colorectal Cancer.bioRxiv : the preprint server for biology · 2026Article
- Uncovering the Intricate and Heterogeneous Cellular Microenvironment of Cutaneous Melanoma.Medicina (Kaunas, Lithuania) · 2026Review
- Mechanisms of immune resistance in microsatellite-stable colorectal cancer.Frontiers in oncology · 2026Review
- FABP5 regulates an immunosuppressive microenvironment in hepatocellular carcinoma through the NF-κB/PD-L1 axis.PloS one · 2026Article
- Rewiring tumor-associated macrophages in hepatocellular carcinoma.Frontiers in immunology · 2026Review
- A two-decade bibliometric analysis of tumor-associated macrophages in colorectal cancer research.Human vaccines & immunotherapeutics · 2025Article
- KLB as a potential prognostic biomarker and therapeutic target in colorectal cancer: insights from multi omics and single cell analyses.Discover oncology · 2025Article
- Targeting tumor-associated macrophages in colon cancer: mechanisms and therapeutic strategies.Frontiers in immunology · 2025Review
- The role of intestinal macrophage polarization in colitis-associated colon cancer.Frontiers in immunology · 2025Review
- Immunological landscape of colorectal cancer: tumor microenvironment, cellular players and immunotherapeutic opportunities.Frontiers in molecular biosciences · 2025Review
- A Critical Role of DC-SIGNImmunoTargets and therapy · 2025Article
- Insights into CSF-1R Expression in the Tumor Microenvironment.Biomedicines · 2024Review
- The Roles of T cells in Immune Checkpoint Inhibitor-Induced Arthritis.Aging and disease · 2024Review
- Targeting the CSF1/CSF1R signaling pathway: an innovative strategy for ultrasound combined with macrophage exhaustion in pancreatic cancer therapy.Frontiers in immunology · 2024Review
- Research Progress on Tumor-Associated Macrophages and PD-1/PD-L1 Inhibitors in Advanced Colorectal Cancer.Cancer control : journal of the Moffitt Cancer CenterReview
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor-associated macrophages (TAMs) and cancer-associated fibroblasts (CAFs) are known to play supportive roles in tumor development and progression, but their interactions in colorectal cancer (CRC) remain unclear. Here, we investigated the effects of colon-cancer-derived CAFs on TAM differentiation, migration, and tumor immunity, both in vitro and in vivo. When co-cultured with monocytes, CAFs attracted monocytes and induced their differentiation into M2 macrophages. Immunohistology of surgically resected human CRC specimens and orthotopically transplanted mouse tumors revealed a correlation between numbers of CAFs and numbers of M2 macrophages. In a mouse model of CRC orthotopic transplantation, treatment with an inhibitor of the colony-stimulating factor-1 receptor (PLX3397) depleted M2 macrophages and increased CD8-positive T cells infiltrating the tumor nest. While this treatment had a minor effect on tumor growth, combining PLX3397 with anti-PD-1 antibody significantly reduced tumor growth. RNA-seq following combination therapy showed activation of tumor immunity. In summary, CAFs are involved in the induction and mobilization of M2 macrophage differentiation in the CRC tumor immune microenvironment, and the combination of cancer immunotherapy and PLX3397 may represent a novel therapeutic option for CRC.
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