ArticleJournal of neuro-oncology2020
Rapamycin and hydroxychloroquine combination alters macrophage polarization and sensitizes glioblastoma to immune checkpoint inhibitors.
Article in Journal of neuro-oncology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 53 citations in OpenAlex.
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- Meningeal immunity and "Interstitial" therapy: a new paradigm for immunotherapy in glioblastoma.Frontiers in immunology · 2026Review
- T cell exhaustion‑related gene CD79B predicts prognosis, inhibits malignant progression and promotes tumor‑associated macrophage M1‑like polarization in lung adenocarcinoma.Oncology reports · 2025Article
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- TSC1 deficiency drives immune evasion in colorectal cancer via mTORC1-mediated dysregulation of PD-L1 sialylation.Frontiers in immunology · 2025Article
- Advances in the treatment of glioma-related signaling pathways and mechanisms by metformin.Frontiers in oncology · 2025Review
- Glypican-3-targeted macrophages delivering drug-loaded exosomes offer efficient cytotherapy in mouse models of solid tumours.Nature communications · 2024Article
- Advances in functional lipid nanoparticles: from drug delivery platforms to clinical applications.3 Biotech · 2024Review
- Understanding current experimental models of glioblastoma-brain microenvironment interactions.Journal of neuro-oncology · 2024Review
- A new perspective on the therapeutic potential of tumor metastasis: targeting the metabolic interactions between TAMs and tumor cells.International journal of biological sciences · 2024Review
- Treatment advances in high-grade gliomas.Frontiers in oncology · 2024Review
- Macrophage metabolism, phenotype, function, and therapy in hepatocellular carcinoma (HCC).Journal of translational medicine · 2023Review
- Overcoming anti-PD-1/PD-L1 immune checkpoint blockade resistance: the role of macrophage, neutrophils and mast cells in the tumor microenvironment.Clinical and experimental medicine · 2023Review
- Macrophage's role in solid tumors: two edges of a sword.Cancer cell international · 2023Article
- Review
- Lipid metabolism reprogramming in tumor-associated macrophages and implications for therapy.Lipids in health and disease · 2023Review
- Turning adversity into opportunity: Small extracellular vesicles as nanocarriers for tumor-associated macrophages re-education.Bioengineering & translational medicine · 2023Review
- Immunosuppressive cells in oncolytic virotherapy for glioma: challenges and solutions.Frontiers in cellular and infection microbiology · 2023Review
- The tumor micro-environment in pediatric glioma: friend or foe?Frontiers in immunology · 2023Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe failure of immune checkpoint inhibitor (ICPi) on glioblastoma (GBM) treatment underscores the need for improving therapeutic strategy. We aimed to change tumor associated macrophage (TAM) from M2 type (anti-inflammatory) to M1 (pro-inflammatory) type to increase the therapeutic response of ICPi. We proposed that combined rapamycin (R) and hydroxychloroquine (Q) preferentially induce M2 cells death, as fatty acid oxidation was their major source of energy.
methodsMacrophage polarization was characterized on mice and human macrophage cell lines by specific cytokines stimulation with or without RQ treatment under single culture or co-culture with GBM cell lines. Tumor sizes were evaluated on subcutaneous and intracranial GL261 mice models with or without RQ, anti-PD1 mAb treatment. Tumor volumes assessed by MRI scan and proportions of tumor infiltrating immune cells analyzed by flow cytometry were compared.
resultsIn vitro RQ treatment decreased the macrophages polarization of M2, increased the phagocytic ability, and increased the lipid droplets accumulation. RQ treatment decreased the expression levels of CD47 and SIRPα on tumor cells and macrophage cells in co-culture experiments. The combination of RQ and anti-PD1 treatment was synergistic in action. Enhanced the intra-tumoral M1/M2 ratio, the CD8/CD4 ratio in the intracranial GL261 tumor model after RQ treatment were evident.
conclusionWe provide a rationale for manipulating the macrophage phenotype and increased the therapeutic effect of ICPi. To re-educate and re-empower the TAM/microglia opens an interesting avenue for GBM treatment.
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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.