| 2020 |
FOLR2 gene expression in macrophages is transcriptionally regulated by the PU.1 transcription factor. PU.1-binding elements were identified upstream of the first exon of FOLR2, and siRNA-mediated knockdown of PU.1 reduced FOLR2 expression in myeloid cells. Functional analysis of the proximal regulatory region of FOLR2 confirmed dependence on a cluster of PU.1-binding sequences. |
siRNA knockdown, luciferase reporter assay of FOLR2 proximal regulatory region, bioinformatic identification of PU.1-binding elements |
Cells |
Medium |
32532019
|
| 2022 |
FOLR2+ tissue-resident macrophages localize in perivascular areas of the tumor stroma in breast cancer, where they physically interact with CD8+ T cells and efficiently prime effector CD8+ T cells ex vivo. |
Immunofluorescence localization, ex vivo co-culture priming assay, flow cytometry |
Cell |
Medium |
35325594
|
| 2016 |
FRβ (FOLR2 protein) is expressed on mature myeloid-lineage hematopoietic cells (including CD14+ monocytes) but is nearly undetectable on CD34+ hematopoietic stem cells, as determined using a high-affinity (2.48 nM KD) FRβ-specific antibody. CAR T cells targeting FRβ lysed mature CD14+ monocytes while leaving HSC colony formation unaffected. |
Flow cytometry with high-affinity FRβ-specific antibody, in vitro cytotoxicity assay, HSC colony formation assay, in vivo xenograft model |
Leukemia |
Medium |
26898190
|
| 2024 |
FOLR2 expression on macrophages is regulated during M-CSF-driven differentiation in skin via intrinsic STAT6 and ALK5 activity, without requiring heterotypic cellular crosstalk. In contrast, CD163 co-expression on the same FRβ/CD163+ S1 macrophage subset requires fibroblast-derived signals (laminin-α2 and type-V collagen) through an SHP1/STAT5-dependent pathway. |
Single-cell transcriptomics, flow cytometry, coculture experiments with fibroblasts, in silico ligand expression analysis, pharmacological inhibition of STAT6/ALK5/SHP1 |
Cellular and molecular life sciences : CMLS |
Medium |
39720957
|
| 2024 |
FOLR2+ macrophages promote fibrosis in chronic kidney disease through a WNT/β-catenin-dependent pathway: inflammatory fibroblasts (CXCL-iFibro) attract and accumulate FOLR2+ macrophages, which in turn drive the switch of CXCL-iFibro into ECM-secreting myofibroblasts via WNT/β-catenin signaling. |
In vitro macrophage-fibroblast coculture, WNT/β-catenin pathway analysis, single-cell transcriptomics, multiplex immunohistochemistry |
Nature communications |
Medium |
38272907
|
| 2018 |
Silencing of FOLR2 in the NCI-H1650 non-small cell lung cancer cell line inhibited phosphorylation of AKT, mTOR, and S6K1, reduced cell viability, arrested cells in G1 phase, decreased cyclin D1, and increased Bax/Bcl-2 ratio and apoptosis. |
siRNA-mediated gene knockdown, Western blot, CCK-8 viability assay, flow cytometry (cell cycle and apoptosis) |
Medical science monitor |
Low |
30415267
|
| 2025 |
FOLR2+ macrophages in breast cancer activate CD8+ T cell cytotoxicity through the CXCL9-CXCR3 axis. FOLR2+ macrophages secrete CXCL9 which engages CXCR3 on CD8+ T cells, and animal experiments confirmed this axis mediates the antitumor effect of FOLR2+ macrophages. |
Single-cell RNA sequencing, bulk RNA sequencing, in vitro coculture, in vivo mouse experiments |
Breast cancer research : BCR |
Medium |
40045365
|
| 2024 |
FOLR2+ macrophages activate CD8+ T cell cytotoxicity via antigen cross-presentation in gastric cancer progression. Epithelial cells induce necroptosis of FOLR2+ macrophages via the APP-TNFRSF21 axis, reducing their proportion from complete intestinal metaplasia to early gastric cancer. |
Single-cell RNA sequencing, multiplex immunohistochemical staining, in vitro coculture of FOLR2+/FOLR2- macrophages with CD8+ T cells, flow cytometry |
Journal of experimental & clinical cancer research : CR |
Medium |
39702278
|
| 2025 |
FOLR2+ macrophages in gastric cancer suppress CD8+ T cell function by expressing PD-L1 and secreting IL-10. Disruption of IL-10 sensitizes anti-PD-1 blockade and promotes antitumor immunity in FOLR2+ TAM-high tumors, demonstrated in fresh tumor tissue culture. |
In vitro culture of fresh tumor tissue, multiplex immunohistochemistry, transcriptional data analysis |
International journal of surgery (London, England) |
Low |
41263393
|
| 2024 |
miR-622 directly targets FOLR2 mRNA to promote colorectal cancer cell proliferation. FOLR2 was validated as a functional target of miR-622 via dual luciferase assay; FOLR2 negatively correlates with cell cycle gene signatures, and its suppression by miR-622 drives cell cycle progression. |
Dual luciferase reporter assay, gain-of-function and loss-of-function experiments in vitro and in vivo, bioinformatics |
BMC cancer |
Medium |
38166756
|
| 2025 |
CLL cells acquire functional FOLR2 protein from nurse-like cells (NLCs) via trogocytosis, enhancing their folate uptake. FOLR2+ CLL cells (those that acquired FOLR2 by trogocytosis) are the predominant actively cycling cancer cell population. This was confirmed by multiplex immunofluorescence in CLL patient lymph nodes. |
Primary patient cell coculture, flow cytometry, multiplex immunofluorescence of lymph node biopsies, proliferation assays |
bioRxivpreprint |
Low |
|
| 2024 |
FOLR2-encoded folate receptor beta (FRβ) was predicted and experimentally validated to bind PFNA, PFOA, and PFOS (but not PFHxS, PFBS, or GenX) by in vitro protein binding analysis, correlating with their in vivo neurodevelopmental toxicity in zebrafish. |
Reverse molecular docking (computational), in vitro protein binding assay, in vivo zebrafish loss-of-function and rescue experiments |
bioRxivpreprint |
Low |
|
| 2026 |
In aging mouse testes, FOLR2+ resident macrophages undergo a phenotypic transition toward a pro-inflammatory state driven by mitochondrial metabolic dysfunction, specifically inhibition of IDH2 (a TCA cycle enzyme). This transition facilitates recruitment of monocytes and CD8+ T cells via the CCL8-CCR2/CCR5 axis. |
Single-cell RNA sequencing, multiplex immunofluorescence, IDH2 inhibition experiments |
GeroScience |
Low |
41618065
|