ArticleCancer research2015
Perivascular M2 Macrophages Stimulate Tumor Relapse after Chemotherapy.
Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 313 papers, 2 of them syntheses 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
313 citing papers in PubMed, 2 syntheses or guidelines pooled it, 521 citations in OpenAlex.
- Tie2 Receptor in Tumor-Infiltrating Macrophages Is Dispensable for Tumor Angiogenesis and Tumor Relapse after Chemotherapy.Cancer research · 2022Pooled it
- Rs-10889677 variant in interleukin-23 receptor may contribute to creating an inflammatory milieu more susceptible to bladder tumourigenesis: report and meta-analysis.Immunogenetics · 2021Pooled it
- Reprogramming tumor-associated macrophages in breast cancer: from myeloid plasticity and tumor-promoting programs to CAR-macrophage therapy.Journal of hematology & oncology · 2026Review
- Portal Vein Tumor Thrombus in Hepatocellular Carcinoma: An Immune Sanctuary Driving Immune Exclusion and Therapeutic Resistance.Liver cancer · 2026Review
- Cytokine Regulation of the Bone Pre- and Metastatic Niches: Implications for Breast Cancer Dormancy.Cells · 2026Review
- Macrophage Plasticity in Cancer Therapy: Function, Timing, and Tradeoffs.International journal of molecular sciences · 2026Review
- The pivotal role of macrophages in tumorigenesis and pioneering cancer immunotherapy across pre-clinical and clinical frontiers.Journal of cancer research and clinical oncology · 2026Review
- Tumor heterogeneity: development, mechanisms, and therapeutic implications.Signal transduction and targeted therapy · 2026Review
- Single-Cell Atlas of Renal Cell Carcinoma Brain Metastasis Uncovers Mechanisms of Immune Dysfunction and Resistance.bioRxiv : the preprint server for biology · 2026Article
- The double-edged sword role of tumor-associated macrophages: preventing or causing resistance to immunotherapy.Journal of experimental & clinical cancer research : CR · 2026Review
- Dual PD-1/IL-2Rα targeting restores CD8Cell reports. Medicine · 2026Article
- Plasminogen Activator Inhibitor-1 Mediates Tolerance to Anti-PD-1 Immunotherapy in Non-Small Cell Lung Cancer.Molecular cancer therapeutics · 2026Article
- PDE4B deficiency aids macrophage differentiation and contributes to Cryptococcus neoformans brain infection.PLoS pathogens · 2026Article
- XOR-mediated tumor-selective nanomaterial therapy: achieving tumor and immune cell dual regulation through intracellular ROS generation.Journal of nanobiotechnology · 2026Article
- Tumor-associated macrophages promote chemoresistance to Paclitaxel via activating NOTCH2-JAG1 juxtacrine signaling.Molecular cancer · 2026Article
- Integration of transcriptomic data reveals lipid metabolic heterogeneity and identifies GSTO1 as a therapeutic target in acute myeloid leukemia.Frontiers in immunology · 2026Article
- Targeting Folate Receptors for the Detection and Selective Treatment of Cancer: Advanced Precision Oncology in Practice.International journal of biological sciences · 2026Review
- Immunity and Beyond: Emerging Roles of Monocytes and Macrophages in Cancer.Advances in experimental medicine and biology · 2026Review
- LAC-TME classifier: machine learning-driven model predicts survival and prioritizes targeted therapy in clear cell renal cell carcinoma.Journal of cancer research and clinical oncology · 2025Article
- Nano MgO loaded thermosensitive HPCH@HA hydrogel accelerates in situ bone repair through osteoimmunomodulation while enhancing angiogenesis and osteogenesis.Bioactive materials · 2025Article
253 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 4 countries.
Funding
Abstract
Tumor relapse after chemotherapy-induced regression is a major clinical problem, because it often involves inoperable metastatic disease. Tumor-associated macrophages (TAM) are known to limit the cytotoxic effects of chemotherapy in preclinical models of cancer. Here, we report that an alternatively activated (M2) subpopulation of TAMs (MRC1(+)TIE2(Hi)CXCR4(Hi)) accumulate around blood vessels in tumors after chemotherapy, where they promote tumor revascularization and relapse, in part, via VEGF-A release. A similar perivascular, M2-related TAM subset was present in human breast carcinomas and bone metastases after chemotherapy. Although a small proportion of M2 TAMs were also present in hypoxic tumor areas, when we genetically ablated their ability to respond to hypoxia via hypoxia-inducible factors 1 and 2, tumor relapse was unaffected. TAMs were the predominant cells expressing immunoreactive CXCR4 in chemotherapy-treated mouse tumors, with the highest levels expressed by MRC1(+) TAMs clustering around the tumor vasculature. Furthermore, the primary CXCR4 ligand, CXCL12, was upregulated in these perivascular sites after chemotherapy, where it was selectively chemotactic for MRC1(+) TAMs. Interestingly, HMOX-1, a marker of oxidative stress, was also upregulated in perivascular areas after chemotherapy. This enzyme generates carbon monoxide from the breakdown of heme, a gas known to upregulate CXCL12. Finally, pharmacologic blockade of CXCR4 selectively reduced M2-related TAMs after chemotherapy, especially those in direct contact with blood vessels, thereby reducing tumor revascularization and regrowth. Our studies rationalize a strategy to leverage chemotherapeutic efficacy by selectively targeting this perivascular, relapse-promoting M2-related TAM cell population.
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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.