ArticleJCI insight2018
Compensation between CSF1R+ macrophages and Foxp3+ Treg cells drives resistance to tumor immunotherapy.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
94 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
- Safety and efficacy of dual PI3K-δ, γ inhibitor, duvelisib in patients with relapsed or refractory lymphoid neoplasms: A systematic review and meta-analysis of prospective clinical trials.Frontiers in immunology · 2022Pooled it
- Ad-SGE-DKK3 Gene Therapy Overcomes Resistance to Immune Checkpoint Blockade in Pleural Mesothelioma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Macrophage Plasticity in Cancer Therapy: Function, Timing, and Tradeoffs.International journal of molecular sciences · 2026Review
- Spatiotemporal dynamics of radioresistance: decoding macrophage-driven radioprotective niches through temporal-spatial reprogramming.Molecular cancer · 2026Review
- Decoding the immune microenvironment: precision immunotherapy for medulloblastoma subtypes.Frontiers in immunology · 2026Review
- Exhausted CD4Frontiers in immunology · 2026Article
- Foxp3Current gene therapy · 2026Article
- Single-cell profiling of peripheral and local immune compartments reveal unique genotype-independent prognostic immune signatures across isocitrate dehydrogenase-stratified glioma.Neuro-oncology · 2026Article
- Tumor-associated macrophages in cancer: from mechanisms to application.Molecular biomedicine · 2025Review
- Targeting CTGF overcomes resistance to CSF1R inhibitors by preventing CAF activation in colorectal cancer.Cell reports. Medicine · 2025Article
- Targeting Myeloid Cells for Cancer Immunotherapy.Cancer immunology research · 2025Review
- Tumor-associated macrophages: untapped molecular targets to improve T cell-based immunotherapy.Molecular cancer · 2025Review
- Role of Colony Stimulating Factor 1 (CSF-1) and Its Receptor CSF1R: Macrophage Repolarization for Glioblastoma Treatment.ACS pharmacology & translational science · 2025Review
- Loss of PI3Kδ Activity Drives Autoimmune Colitis by Impairing Extrathymic Treg Differentiation.European journal of immunology · 2025Article
- Loss of PI3Kδ Activity Drives Autoimmune Colitis by Impairing Extrathymic Treg Differentiation.European journal of immunology · 2025Article
- JMC14: a novel dual PI3Kδ/CSF1R inhibitor with potent antitumor activity in hematological and solid tumors.Acta pharmacologica Sinica · 2025Article
- Anoikis resistance in Cancer: Mechanisms, therapeutic strategies, potential targets, and models for enhanced understanding.Cancer letters · 2025Review
- Macrophages in prostate cancer: dual roles in tumor progression and immune evasion.Journal of translational medicine · 2025Review
- Tumor-associated macrophages remodel the suppressive tumor immune microenvironment and targeted therapy for immunotherapy.Journal of experimental & clinical cancer research : CR · 2025Review
- Myeloid cells: key players in tumor microenvironments.Frontiers of medicine · 2025Review
34 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
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Redundancy and compensation provide robustness to biological systems but may contribute to therapy resistance. Both tumor-associated macrophages (TAMs) and Foxp3+ regulatory T (Treg) cells promote tumor progression by limiting antitumor immunity. Here we show that genetic ablation of CSF1 in colorectal cancer cells reduces the influx of immunosuppressive CSF1R+ TAMs within tumors. This reduction in CSF1-dependent TAMs resulted in increased CD8+ T cell attack on tumors, but its effect on tumor growth was limited by a compensatory increase in Foxp3+ Treg cells. Similarly, disruption of Treg cell activity through their experimental ablation produced moderate effects on tumor growth and was associated with elevated numbers of CSF1R+ TAMs. Importantly, codepletion of CSF1R+ TAMs and Foxp3+ Treg cells resulted in an increased influx of CD8+ T cells, augmentation of their function, and a synergistic reduction in tumor growth. Further, inhibition of Treg cell activity either through systemic pharmacological blockade of PI3Kδ, or its genetic inactivation within Foxp3+ Treg cells, sensitized previously unresponsive solid tumors to CSF1R+ TAM depletion and enhanced the effect of CSF1R blockade. These findings identify CSF1R+ TAMs and PI3Kδ-driven Foxp3+ Treg cells as the dominant compensatory cellular components of the immunosuppressive tumor microenvironment, with implications for the design of combinatorial immunotherapies.
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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.