Stromal FOXF2 suppresses prostate cancer progression and metastasis by enhancing antitumor immunity

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Cancer-associated fibroblasts (CAFs) contribute to an immunosuppressive tumor microenvironment.
• The precise mechanisms by which CAFs suppress anti-tumor immunity are not fully understood.

Purpose of the Study:

• To investigate the role of the transcription factor Foxf2 in the prostatic stroma.
• To elucidate the impact of stromal Foxf2 on prostate cancer progression and the tumor immune microenvironment.

Main Methods:

• Utilized syngeneic and autochthonous mouse prostate cancer models.
• Analyzed the effects of Foxf2 on CAF phenotype and gene expression (Cxcl5).
• Assessed immune cell populations (myeloid cells, T cells) and T cell cytotoxicity.
• Examined human prostate tissues for FOXF2 expression and correlation with Gleason grade.

Main Results:

• Increased prostatic stromal Foxf2 suppressed prostate cancer growth in immunocompetent mice.
• Foxf2 attenuated CAF phenotype and downregulated Cxcl5, reducing immunosuppressive myeloid cells.
• Foxf2 enhanced T cell cytotoxicity and sensitized prostate cancer to immune checkpoint blockade.
• Elevated stromal FOXF2 in human transition zone prostate and inversely correlated with Gleason grade.

Conclusions:

• Stromal Foxf2 acts as a key regulator of the tumor immune microenvironment in prostate cancer.
• Foxf2 modulation offers a potential strategy to enhance anti-tumor immunity and improve treatment efficacy.
• Higher FOXF2 in the transition zone may contribute to the lower incidence and indolent nature of prostate cancers in this region.