. Combined radiotherapy and histamine for effective treatment of breast cancer

STERLE HA; CREMASCHI G; NICOUD M; HERRERO DUCLOUX, MARÍA V.; MEDINA VA; MARTINEL LAMAS D; MASSARI NA; BLANCO H

BUENOS AIRES

Congreso; Reunión Conjunta de Sociedades de Biociencias - LXII Reunión Anual de la SAIC, Sociedad Argentina de Investigación Clínica; 2017

Previous studies demonstrated that histamine enhanced ionizing radiation (IR)-induced response in vitro and in vivo in human triple negative breast cancer (TNBC) and melanoma models. The aim of this work was to further explore the effect of the combination treatment of histamine and gamma IR ontumor immunity, employing a syngeneic TNBC model,withintactimmune system, developed in Balb/c mice with 4T1 cells.Proliferation, apoptosis and oxidative damage studies were performed.Tumor infiltrating lymphocytes and lymphocyte subpopulations in spleen were evaluated by FACS.Results indicate that histamine potentiates IR response mainly in vivo.Radiation administered as 3 doses of 2 Gy in consecutive daysreduced tumor growth and weight. Treatment of 4T1 tumor-bearing mice with histamine (1 mg/kg.day) injected scstarting 1 day before irradiation until the end of the experiment, potentiated IR-induced decrease in tumor growth (P˂0.05)and also reduced splenomegaly. The analysis of the distribution of the immune cell subsets showed decreased CD4+ and CD8+ T together with reduced CD19+ B lymphocytes in both histamine-treated and non-treated irradiated tumors. Conversely, histamine treatment increased the percentages of NK cells (4.6±0.8 vs. 1.7±0.3, P˂0.01)and myeloid derived stem cells (26.7±3.8 vs. 8.9±1.0, P˂0.05)in irradiated tumors. Non-significant changes in the percentage of lymphocyte populations were observed in spleen of tumor-bearing animals. We conclude that histamine could improve radiation therapy in part by modulating tumor immunity.