Can Reproductive Hormones Modulate Host Immunity to Breast Cancer Antigens

摘要

HER-2/neu (neu) transgenic mice (neu-N mice) overexpress the neu proto-oncogene in a mammary specific fashion and develop spontaneous neuexpressing mammary neoplasia. The neu-N mouse model is among the most informative pre-clinical models available for the development of vaccine strategies for the treatment and prevention of breast cancer. The goal of this proposal was to test the hypothesis that reproductive hormones can modulate immunity to breast cancer antigens in neu-N mice. We explored this hypothesis by assessing vaccine-induced anti-tumor T cell responses at discreet stages in the mouse estrous cycle, as well as during mammary gland involution. Using these assays, we were unable to demonstrate a clear link between anti-tumor immune modulation and reproductive hormones. However, we were able to make very important discoveries regarding the activation and subsequent attenuation of breast cancer-specific CD8+ cytotoxic T cells in response to vaccination. These data provide important insight into mechanisms of immune tolerance that limit anti-tumor immunity.