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Immune Surveillance by NK Cells and Phagocytes01:25

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Folate receptor β performs an immune checkpoint function in activated macrophages.

Fenghua Zhang1, Md Yusuf Al-Amin1,2, Sagar Utturkar3

  • 1Department of Chemistry and Institute for Drug Discovery, Purdue University, West Lafayette, IN, United States.

Frontiers in Immunology
|October 15, 2025
PubMed
Summary
This summary is machine-generated.

The folate receptor beta (FRβ) acts as an immune checkpoint, regulating myeloid cell function. Deleting FRβ in mice reduces tumor growth and autoimmune symptoms by enhancing pro-inflammatory responses.

Keywords:
MDSCs (myeloid-derived suppressor cells)cancer immunotherapyfolate receptor beta (FRβ, Folr2)immune checkpointmacrophage polarizationmacrophagestumor microenvironmenttumor-associated macrophages (TAMs)

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Area of Science:

  • Immunology
  • Cancer Biology
  • Molecular Biology

Background:

  • Monocytes and macrophages express folate receptor beta (FRβ), a unique immune cell marker.
  • FRβ binding to folate is regulated by immunosuppressive cytokines, suggesting a potential immune function.

Purpose of the Study:

  • To investigate the immune-related function of FRβ.
  • To determine FRβ's role in autoimmune diseases and tumor immunity.

Main Methods:

  • Comparison of wild-type (WT) and FRβ knockout (KO) mice.
  • Analysis of autoimmune symptoms, tumor growth, and immune cell populations in tumors.
  • Gene expression analysis of bone marrow-derived macrophages.
  • In vitro studies of macrophage-T cell interaction.

Main Results:

  • FRβ KO mice exhibit autoimmune symptoms (alopecia, dermatitis) and slower tumor growth.
  • KO tumors show increased CD69+ T cells and decreased PD1+ T cells and PD-L1+ myeloid cells.
  • FRβ deletion upregulates pro-inflammatory genes and downregulates anti-inflammatory genes in macrophages.
  • FRβ blockade or deletion impairs macrophage-mediated suppression of T cell activation.

Conclusions:

  • FRβ functions as an immune checkpoint regulating myeloid cell immunologic properties.
  • FRβ plays an immunosuppressive role in tumor immunity.
  • FRβ may have a similar immunosuppressive function in human cancers, correlating inversely with survival.