Effects of hormone receptor activation on tumor associated dendritic cell signaling (TUM4P.921)

Abstract

Abstract Gender disparity 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 gender is unclear. Some of the most successful cancer therapies to date have focused on hormone receptor blockade in tumor cells. Immune suppression is a major hurdle to overcome in the effort to find an effective and durable treatment against cancer. The underlying causes of immune suppression are complex and not completely understood. Hormones, including androgen and estradiol, are also known to dampen immune responses, but immune suppression or activation has not been studied during hormone deprivation therapy. Many studies indicate that tumor-associated dendritic cells within the tumor microenvironment are key regulators of cytotoxic T cell function and may serve as a critical target for immunotherapy. Therefore, in the current study, we demonstrate that hormone receptor signaling, androgen receptor and estrogen receptor in dendritic cells has a critical impact on the transcriptional regulation of factors known to induce immune suppression and may be a key factor to consider when designing immune therapies. Furthermore, the data may also implicate the patient’s gender as an important consideration in boosting anti-tumor immune responses.