ArticleFrontiers in immunology2024
Tumor-specific activation of folate receptor beta enables reprogramming of immune cells in the tumor microenvironment.
Article in Frontiers in immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 8 citations in OpenAlex.
- Folate metabolism in tumor-associated macrophages drives immunosuppressive function to promote tumor growth.bioRxiv : the preprint server for biology · 2026Article
- Construction of a risk model based on folate metabolism-related genes to predict prognosis and immunological characteristics of stomach adenocarcinoma.Discover oncology · 2026Article
- IFITM3 promotes an M2-like tumor-supportive microenvironment in acute myeloid leukemia.Medical oncology (Northwood, London, England) · 2026Article
- Folate receptor beta targeting of tumor-associated macrophages improves lymphoma cell responses to CD19 CAR T cells.HemaSphere · 2026Article
- Folate receptor beta drives NLRP3 inflammasome activation and pyroptosis in macrophages independent of folate binding.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Nonglycosylated, Legumain-Cleavable ISACs Drive Potent Antitumor Immunotherapy via a Bystander Effect.Molecular cancer therapeutics · 2026Article
- Surface-Modified Polymeric Nanoparticles for Glioblastoma Therapy: A Review on Targeting Strategies and Delivery of Repurposed Drugs and Off-Label Non-Alkylating Agents.Pharmaceutics · 2026Review
- Targeting Folate Receptors for the Detection and Selective Treatment of Cancer: Advanced Precision Oncology in Practice.International journal of biological sciences · 2026Review
- The Problem of Molecular Target Choice for CAR-T Cells in Acute Myeloid Leukemia Therapy.International journal of molecular sciences · 2025Review
- FOLR2Cell communication and signaling : CCS · 2025Review
- Folate receptor β performs an immune checkpoint function in activated macrophages.Frontiers in immunology · 2025Article
- Advance in therapies targeting tumor-associated macrophages in ovarian cancer.Frontiers in immunology · 2025Review
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Folate receptors can perform folate transport, cell adhesion, and/or transcription factor functions. The beta isoform of the folate receptor (FRβ) has attracted considerable attention as a biomarker for immunosuppressive macrophages and myeloid-derived suppressor cells, however, its role in immunosuppression remains uncharacterized. We demonstrate here that FRβ cannot bind folate on healthy tissue macrophages, but does bind folate after macrophage incubation in anti-inflammatory cytokines or cancer cell-conditioned media. We further show that FRβ becomes functionally active following macrophage infiltration into solid tumors, and we exploit this tumor-induced activation to target a toll-like receptor 7 agonist specifically to immunosuppressive myeloid cells in solid tumors without altering myeloid cells in healthy tissues. We then use single-cell RNA-seq to characterize the changes in gene expression induced by the targeted repolarization of tumor-associated macrophages and finally show that their repolarization not only changes their own phenotype, but also induces a proinflammatory shift in all other immune cells of the same tumor mass, leading to potent suppression of tumor growth. Because this selective reprogramming of tumor myeloid cells is accompanied by no systemic toxicity, we propose that it should constitute a safe method to reprogram the tumor microenvironment.
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