The influence of androgen receptor signaling on male sex-bias in HNSCC

Presenters/Authors(s)

Samantha Antol, Jennifer Franko, Quinn Hopen

Abstract or Description

Sex-biases in head and neck squamous cell carcinoma (HNSCC) have been identified with males exhibiting higher incidence and mortality rates than females. Anti-tumor immunity is known to be an important regulator of tumor onset and progression. Sex biases in HNSCC anti-tumor immunity have previously been identified using a syngeneic model of HNSCC, where male and female C57BL/6 mice were injected orthotopically (tongue) with murine oral squamous cell carcinoma cells (MOC1). Male syngeneic tumor volumes were found to be larger and to have lower CD8+ T cell infiltrates than female tumors.  Castration enhanced CD8+ tumor infiltrates in males to levels similar to that of females and decreased male tumor volumes, suggesting a role for androgens in HNSCC sex biases. We hypothesized that signaling via the androgen receptors (AR) expressed on CD8+ T-cells suppressed their anti-tumor function.  However, we did not know whether MOC1 cells were also responsive to AR signaling.  AR expression by MOC1 tumor cells was confirmed using western blot analysis and immunohistochemistry (IHC) using MOC1 cell lysates and MOC1 syngeneic tumor sections, respectively. Nuclear translocation of AR and  gene expression changes in response to dihydrotestosterone (DHT) exposure were evaluated in in vitro studies, utilizing western blot, flow cytometry and RNAseq, to determine if the AR was functional in MOC1 cells.  By identifying the cause of male sex-biases in HNSCC, better targeted therapeutics can be created for patients with HNSCC.