Abstract ES6-1: Immunotherapeutic approaches to breast cancer

Abstract

Abstract There has been increasing interest in the field of immunooncology with the approval of a therapeutic cancer vaccine for prostate cancer and checkpoint inhibitors targeting CTLA-4 and PDL-1 for the treatment of advanced stage melanoma and lung cancer. These therapies stimulate the “adaptive” immune system. Adaptive immunity requires T-cells and antibodies to directly recognize specific proteins expressed on tumor cells. Recognition of immunogenic cancer associated proteins, known as “antigens”, allows specificity of the immune response to the tumor. Harnessing the immune system to treat cancer has several major advantages over other standard therapies. The T-cells capable of recognizing and killing tumor cells will persist in lymph nodes for years and will be poised to attack antigen expressing tumor when it recurs. T-cells, once primed to react to specific antigens, will traffic out of the circulation and can penetrate into tumor, killing tumor cells as long as they are present. Breast cancer is an immunogenic tumor. In fact, many of the favorable immune characteristics that are present in more classically immunogenic tumors, such as melanoma, are operative in breast cancer. Numerous tumor antigens have been identified in breast cancer. Antibodies directed against tumor antigens are generated very early in the disease process. Breast cancer patients mount immune responses against such proteins as HER-2/neu, IGF-IR, and topoisomerase II alpha to name a few. Further, large numbers of specific types of lymphocytes infiltrating breast cancers have been shown to have prognostic importance in some subtypes of the disease. However, mechanisms of tumor immune escape are also prevalent in breast cancer. Regulatory T-cells which secrete cytokines to prevent the function of cytotoxic T-cells are increased in the tumors of breast cancer patients. High levels of T-regulatory cells indicate poorer outcomes particularly in patients with estrogen receptor positive disease. Type II immune responses, associated with antibody production inhibit the function of Type I T-cells including cytotoxic T-cells needed for tumor eradication. Breast cancers have been shown to up regulate PD-L1 an immune checkpoint protein that prevents T-cells from effectively recognizing and eliminating tumors. A variety of immune therapies are being actively explored for the treatment of breast cancer. However, a more detailed understanding of the breast cancer immune microenvironment must guide how we approach the clinical application of immune therapy. Only a small fraction of patients have robust levels of tumor infiltrating T-cells. Therapeutic approaches aimed at blocking immune checkpoints may be more effective in these patients than in the majority of individuals with little or no pre-existent immunity. Many of the standard therapies that are used in the treatment of breast cancer today have potent immune stimulatory properties. This realization, along with a better understanding of the endogenous immune response in breast cancer, may allow more effective application of combination immunotherapeutic approaches for this disease. Citation Format: Mary L Disis. Immunotherapeutic approaches to breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr ES6-1.