FOSL2 Regulates PD-L1 and Modulates Hormone Therapy Response Heterogeneity.

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Prostate cancer (PCa) treatment response to androgen-targeted therapy is variable.
• Tumor microenvironment, especially tumor-infiltrating lymphocytes (TILs), critically impacts treatment outcomes.
• Previous research highlighted TILs' role in neoadjuvant androgen deprivation therapy (NADT) efficacy.

Purpose of the Study:

• Investigate the interplay between TILs and PCa cells in shaping treatment response.
• Elucidate the molecular mechanisms linking FOSL2, PD-L1, and T cell modulation.
• Identify potential therapeutic targets to overcome treatment resistance.

Main Methods:

• Analysis of publicly available clinical datasets.
• In vitro co-culture systems of T cells and PCa cells.
• Murine xenograft models for in vivo validation.

Main Results:

• Observed dynamic changes in TILs populations during treatment.
• Found concordant expression patterns of FOSL2 and PD-L1.
• Demonstrated FOSL2 directly upregulates PD-L1 expression by binding to its promoter.
• Showed that targeting FOSL2 enhances antitumor effects in combination therapy.

Conclusions:

• FOSL2 contributes to treatment response heterogeneity by modulating the tumor immune microenvironment.
• FOSL2-mediated PD-L1 regulation impacts T cell infiltration and function.
• Targeting FOSL2 offers a potential strategy to enhance androgen-targeted therapy efficacy in PCa.