Abstract B9: Abnormalities in cellular and humoral immunity in breast cancer patients resistant to endocrine therapy.

Abstract

Abstract Defects in the immune response correlated with poor prognosis and therefore in recent years, research focused on a precise description of the status and function of the immune system and its possible effect in cancer patients. Although more than 2/3 of treated patients respond to the endocrine therapy, most patients with metastatic breast cancer will develop resistance.. It appears that other factor contributing to the resistance may be a transforming factor-beta (TGF-beta). It is highly immunosuppressive factor that inhibits the natural and specific immunity against tumors and stimulates production of vascular endothelial growth factor /VEGF. The purpose of the study was to monitor immune responses in patients with hormone receptor positive breast cancer resistant to hormone therapy, particularly the examination of cellular (CD4, CD8, HLA-DR) as well as humoral immunity. TGF beta, and VEGF production was monitored and we analyzed the changes during hormonal treatment. Methods: 85 patients included in the research project were implemented routine cancer treatment with endocrine therapy. Basic parameters (histological type and grade, the degree of expression of ER and PR, 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, VEGF were measured by ELISA and anti-tumor cellular immunity (CD4, CD8, antigen presenting cells ) were measured by flow cytometry. Results In patients with resistance to endocrine therapy mainly depression in cellular immunity was found. Immunglobulin plasma level was decreased as well (mainly IgG4 subtype). Most patients have shown clinical symptoms of immunodeficiency (frequent infections of respiratory or urinary tract, herpetic infections) TGF beta as well as VEGF plasma level were increased. Significant increase of autoantibodies production was found, particularly in those, involved into blood coagulation process/anti phospholipide and anti cardiolipin autoantibodies. Conclusion Correlation of these factors with resistance to hormonal therapy, and the state of anticancer immunity could help in the future with the prediction of resistance to hormonal therapy and contribute to the selection of targeted immune therapy in cancer patients. Dedication: This project was supported by grant IGA NT11168-3/2010. Citation Format: Eva Zavadova, Bohuslav Konopasek, Michal Vocka, Michaela Miskovicova, Jan Spacek, Terezie Fucikova, Lubos Petruzelka. Abnormalities in cellular and humoral immunity in breast cancer patients resistant to endocrine therapy. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B9.