Gender and alcohol differentially influence DC signaling and ability to initiate an anti-tumor immune response. (TUM10P.1026)

Abstract

Abstract Gender disparity and effect of alcohol has been observed in cancer in relation to incidence, disease aggressiveness and prognosis. However, the role of the immune system and the activation of an anti-tumor immune response based on these parameters are unclear. Ethanol is known to reduce the DC’s ability to present antigen in the setting of an infection, but the signaling mechanisms effected to regulate DC functions which maybe critical in cancer are unclear. Some of the most successful cancer therapies to date have focused on hormone receptor blockade in tumor cells. Hormones, including androgen and estradiol, can dampen immune responses, but immune suppression or activation has not been studied during hormone deprivation therapy or upon previous exposure to alcohol. Tumor-associated dendritic cells (TADC) are key regulators of cytotoxic T-cell (CTL) function and may serve as a critical target for immunotherapy. Therefore, in the current study, we sought to determine the effect of alcohol on hormone receptor signaling, androgen receptor (AR) and estrogen receptor (ER), in TADC. The changes in regulation of these signaling pathways have a critical impact on the transcriptional and translational regulation of factors known to induce immune suppression and may be a key factor to consider when designing immune therapies for cancer.