COMBINED RADIOTHERAPY AND HISTAMINE FOR EFFECTIVE TREATMENT OF BREAST CANCER

MARTINEL LAMAS DJ; NICOUD, MB; STERLE HA; MASSARI NA; HERRERO DUCLOUX, MA; CREMASCHI GA; BLANCO H; MEDINA VA

CABA

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Previous studies demonstrated that histamine enhanced ionizingradiation (IR)-induced response in vitro and in vivo in human triplenegative breast cancer (TNBC) and melanoma models. The aim ofthis work was to further explore the effect of the combination treatmentof histamine and gamma IR on tumor immunity, employing asyngeneic TNBC model, with intact immune system, developed in Balb/c mice with 4T1 cells. Proliferation, apoptosis and oxidativedamage studies were performed. Tumor infiltrating lymphocytes andlymphocyte subpopulations in spleen were evaluated by FACS.Results indicate that histamine potentiates IR response mainly invivo. Radiation administered as 3 doses of 2 Gy in consecutive daysreduced tumor growth and weight. Treatment of 4T1 tumor-bearingmice with histamine (1 mg/kg.day) injected sc starting 1 day beforeirradiation until the end of the experiment, potentiated IR-induceddecrease in tumor growth (P˂0.05) and also reduced splenomegaly.The analysis of the distribution of the immune cell subsets showeddecreased CD4+ and CD8+ T together with reduced CD19+ B lymphocytesin both histamine-treated and non-treated irradiated tumors.Conversely, histamine treatment increased the percentagesof NK cells (4.6±0.8 vs. 1.7±0.3, P˂0.01) and myeloid derived stemcells (26.7±3.8 vs. 8.9±1.0, P˂0.05) in irradiated tumors. Non-significantchanges in the percentage of lymphocyte populations wereobserved in spleen of tumor-bearing animals. We conclude that histaminecould improve radiation therapy in part by modulating tumorimmunity.