Abstract 2327: Boosting cancer vaccine efficacy with Vitamin E for immunoprevention of ER- breast cancer

Abstract Estrogen receptor negative (ER-) breast cancers have worse prognoses with no effective prevention strategies. Developing safe and effective tactics for immunoprevention of poorly immunogenic breast cancers is highly challenging. Recently, we found that vitamin E (VitE) stimulates dendritic cell (DC) functions and potentiates anti-tumor immunity of immunotherapies. Here, we explored whether VitE can enhance anti-tumor immunity of cancer vaccines for immunoprevention of ER- breast cancer. Indeed, VitE, delivered as a vaccine adjuvant, significantly increases dendritic cell antigen presentation and boosts potent antigen-specific T cell responses. We noted that local injection of VitE with vaccines yielded substantially higher efficacy than oral VitE administration Moreover, compared to the vehicle-treated and vaccine only groups, VitE, given as vaccine adjuvants, significantly delayed tumor outgrowth and extended tumor-free survival in multiple mammary tumor transplantation models and in spontaneous mammary tumor model of MMTV-neu transgenic mice, whereas anti-PD1 administration showed a marginal effect in these tumor models. Mechanistically, in addition to targeting DC checkpoint SHP1, VitE fosters antigen uptake, increases co-stimulatory molecules CD80/CD86/CD40 expression and downregulates PD-L1 in DCs, that ultimately boosts antigen-specific effector/memory T cells. Furthermore, VitE administration altered landscapes of CD8+ effector T cells and fostered their transition to memory T cells. Together, our study demonstrates that VitE potentiates cancer vaccine efficacy via DCs and memory T cells, thus can be given as a safe and effective adjuvant of cancer vaccine for immunoprevention of ER- breast cancer. Citation Format: Yi Xiao, Yuan Zhang, Yunhai Li, dihua Yu. Boosting cancer vaccine efficacy with Vitamin E for immunoprevention of ER- breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2327.