The Multifaceted Role of Androgen Receptor Signaling in Immunity: Implications for Oncology

Area of Science:

• Immunology
• Endocrinology
• Oncology

Background:

• Androgen receptor (AR) signaling is traditionally linked to prostate and testis functions.
• AR signaling exerts significant immunomodulatory effects across various immune cell types.
• AR signaling contributes to sex-based differences observed in autoimmunity, infections, and cancer.

Purpose of the Study:

• To review the functional effects of AR signaling in innate and adaptive immune cells.
• To discuss the clinical relevance of modulating AR signaling for immune enhancement, particularly in cancer treatment.
• To assess the translatability of mouse model findings to human immune function.

Main Methods:

• Review of existing literature on AR signaling in immune cells.
• Analysis of data from mouse models with altered androgen signaling (castration, testicular feminization, cell-specific AR knockout).
• Examination of epidemiological and correlative human studies.

Main Results:

• AR signaling influences both innate and adaptive immunity through direct and indirect mechanisms.
• Mouse models provide insights into cell-intrinsic and -extrinsic AR effects on immunity.
• The precise molecular mechanisms of AR's immunomodulatory effects require further elucidation.

Conclusions:

• Modulating AR signaling holds potential for augmenting immune function and treating immune-related diseases, including cancer.
• Further research is needed to clarify molecular mechanisms and confirm human relevance of findings from animal models.
• Clinical efforts are underway to leverage AR signaling modulation for enhanced antitumor immunity.