Cellular and humoral immunodeficiency in breast cancer patients resistant to hormone therapy

Abstract

In view of the fact that insufficiency in immune response often correlates with poor prognosis, research in recent years has focused on the task of describing the precise status and function of the immune system and its possible effect on cancer patients. Although more than two thirds of treated patients respond to endocrine therapy, most patients with metastatic breast cancer develop a resistance to it. Estrogen modulates angiogenesis, partially through its effects on vascular endothelial growth factor (VEGF). It also appears that transforming growth factor-beta (TGF beta) could be another factor contributing to this resistance. TGF beta is a highly immunosuppressive factor that inhibits natural and specific immunity against tumors and stimulates the production of VEGF. The purpose of the study was to monitor immune responses in patients with hormone receptor-positive breast cancer who were resistant to hormone therapy. The examination of cellular components (CD4, CD8, HLA-DR, NK cells) and humoral immunity (IgG, IgG subclasses, IgA, IgM,). TGF beta and VEGF production were monitored with special attention, along with an analysis of the changes that occurred during the hormonal treatment. 68 patients included in the research project were implemented with routine cancer treatment with endocrine therapy. Basic parameters (the histological type and grade, the degree of expression of estrogen receptors (ER) and progesterone receptors (PR), human epidermal growth factor receptor 2 (HER2), and the proliferative marker) were established. Patients were evaluated by a cancer clinical immunologist to exclude immune disorders, allergic or autoimmune origin. TGF beta and VEGF were measured by ELISA and antitumor cellular immunity (CD4, CD8) was measured by flow cytometry. Patients who failed in the first line of hormone therapy treatment were considered as resistant to hormone therapy.Depression in cellular immunity was found especially in patients with resistance to endocrine therapy. In addition, immunoglobulin plasma levels were decreased (mainly IgG4 subtype). Most patients showed clinical symptoms of immunodeficiency (frequent infections of respiratory or urinary tract, herpetic infections). Significant increases in TGF beta and VEGF plasma were also detected.The correlation of these factors with resistance to hormonal therapy and the state of anticancer immunity could be helpful in the task of predicting resistance to hormonal therapy and could contribute to the selection of targeted immune therapy in cancer patients in the future.