Abstract 611: Sex disparities in cancer immunoediting

Abstract

Abstract Cancer immunoediting is the process through which tumor specific T cell populations both prevent cancer development and apply selective pressure for the outgrowth of less immunogenic tumors with reduced neoantigen burden. Male and female immune systems demonstrate distinct differences that drive characterized disparities in response to viral infection and immunization. While several recent publications have shown that anti-tumor immune responses are inhibited by male sex hormone signaling, a critical gap in knowledge exists surrounding sex-based differences in the larger-scale process of immunoediting. Because the residual neoantigen burden expressed after tumor escape from immune surveillance is an important determinant of rejection following immune checkpoint blockade, disparities in immunoediting between males and females could have profound impacts on both cancer incidence and response to therapy. The purpose of our studies is to determine if the enhanced functionality of female T cells results in more effective immunoediting of tumors that evolve in females versus those that evolve in males. We have used the 3-methylcholanthrene carcinogen-induced tumor model and several transplant tumor models to determine if T cell function regulates differential cancer development between the sexes. We have also analyzed predicted neoantigen burden in male and female patients with melanoma and lung cancer to identify sex-based differences in tumor immunogenicity. We have found that female T cell responses are more effective at preventing tumor occurrence and delaying tumor outgrowth compared to male T cell responses in mice, which may help to explain established sex-based disparities in cancer incidence in the human population. In comparison, male patient tumors were more likely to express high neoantigen burden compared to their female counterparts. These results suggest that while stronger anti-tumor T cell responses in females are helpful in driving lower cancer incidence in females compared to males, this disparity may also result the development of tumors that express greater numbers of immunogenic neoantigens in males versus females. A better understanding of how sex impacts the entire process of immunoediting will help to explain cancer disparities between the sexes and identify potential new therapeutic strategies that can benefit all patients. Citation Format: Katey Hunt, Elise Alspach. Sex disparities in cancer immunoediting [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 611.