FR-β
FR-β (folate receptor beta, FOLR2) is a glycosylphosphatidylinositol-anchored folate-binding receptor that mediates high-affinity folate uptake in cells of the myeloid lineage and activated macrophages[1][2]. Its biological function is closely linked to macrophage differentiation and polarization, where FR-β expression increases folate internalization capacity and reflects specialized immune programs within tissue-resident and activated macrophage populations[1][3]. Mechanistically, FR-β is preferentially induced by M-CSF and maintained by anti-inflammatory cytokine signaling, whereas GM-CSF and IFN-γ suppress its expression, establishing a connection between FR-β activity and M2-like macrophage polarization[1]. In disease settings, FR-β is detected in tumor-associated macrophages, synovial macrophages from rheumatoid arthritis, and other inflammatory myeloid populations, making it a valuable marker for studying macrophage-driven immune regulation and tissue inflammation[1][4]. Compared with related folate receptor isoforms, FR-α (FOLR1) is predominantly expressed in epithelial tissues and many epithelial cancers, whereas FR-β displays a more restricted distribution centered on activated monocytes and macrophages, providing greater specificity for myeloid-cell-focused investigations[2][5]. This isoform distinction has supported the development of FR-β-targeted imaging agents, antibodies, and folate-conjugated therapeutics that selectively deliver payloads to activated macrophages or tumor-associated macrophages in experimental models[1][4][6]. Therefore, FR-β serves as both a functional regulator of folate uptake and a translational target for macrophage tracking, immune microenvironment analysis, and targeted therapeutic research[1][3][6].
References:
- [1]. Puig-Kröger A, et al. Folate receptor beta is expressed by tumor-associated macrophages and constitutes a marker for M2 anti-inflammatory/regulatory macrophages. Cancer Res. 2009 Dec 15;69(24):9395-403. [Content Brief]
- [2]. Shen J, et al. Assessment of folate receptor-β expression in human neoplastic tissues. Oncotarget. 2015 Jun 10;6(16):14700-9. [Content Brief]
- [3]. Samaniego R, et al. Folate Receptor β (FRβ) Expression in Tissue-Resident and Tumor-Associated Macrophages Associates with and Depends on the Expression of PU.1. Cells. 2020 Jun 10;9(6):1445. [Content Brief]
- [4]. Chubinskaya S, et al. Regulation of chondrocyte gene expression by osteogenic protein-1. Arthritis Res Ther. 2011 Mar 29;13(2):R55. [Content Brief]
- [5]. Khalili M, et al. Underserved Does Not Mean Undeserved: Unfurling the HCV Care in the Safety Net. Dig Dis Sci. 2018 Dec;63(12):3250-3252. [Content Brief]
- [6]. Deng B, et al. Peripheral leukemia burden at time of apheresis negatively affects the clinical efficacy of CART19 in refractory or relapsed B-ALL. Mol Ther Methods Clin Dev. 2021 Oct 27;23:633-643. [Content Brief]
