Immunity and autoimmunity in breast cancer

Abstract

Evading immune destruction should be considered an emerging hallmark of cancer [1]. Highly immunogenic cancer cells can be eliminated in immunocompetent hosts as a result of the immunoediting process. Weakly immunogenic variants can grow and generate solid tumours. Regulatory T cells (Tregs) were found to be involved in the maintenance of the immune tolerance both preventing autoimmune disease and curtailing antitumour immune response. Modulation of immune response in cancer patients is the result of a balanced activity of Tregs and T-effector cells [2]. In cancer patients, an increased number of Tregs was found in blood and tumour tissue: it was demonstrated that Tregs suppress T-cell response and natural killer cell proliferation and function, thus interfering both with acquired and innate immunity. Upregulation of Tregs in the tumour bed can be associated with worse prognosis [3]. Drugs blocking function of Tregs increase activity of T effectors and, as a side effect, induce an autoimmune disease. Issues of biology and prognosis of breast cancer in the presence of a deregulation of the immune system need to be studied. The identification of immunological and genetic features affecting immune response in patients with minimal tumour burden is the optimal background for development of clinical studies in the adjuvant setting. Research on tumour-associated antigens (TAAs) has identified a large collection of peptide epitopes that have been and are being used for vaccination of cancer patients [4]. Several potential advantages of using peptide-based vaccines include: easy and relatively inexpensive production of synthetic peptides; the easy administration of peptides in a clinical setting; the possibility of treating only those patients whose tumours overexpress the target antigens; and the availability of in vitro or ex vivo assays that can assess patients' immune response to vaccine epitopes. The aim of future studies will be to assess the immunoreactivity of several antigens in a large series of breast cancer samples classified according to molecular subtypes. Identification of potential targets in subpopulations of patients with breast cancer may allow identification of patients who are potential candidates for adjuvant therapeutic vaccines. It is our current thinking that patients with minimal residual disease after preoperative chemotherapy are the ideal setting to test the efficacy of a vaccination strategy. To date, vaccines for breast cancer have been mainly used in end-stage disease. TAA antigens offer a novel opportunity for fostering vaccine development and therapy.