IMMUNOMODULATORY ROLES OF HISTAMINE H4 RECEPTOR IN BREAST CANCER

STERLE HA; NICOUD, MB; MASSARI NA; TÁQUEZ DELGADO, MA; HILDEBRANDT X; HERRERO DUCLOUX, MA; CREMASCHI GA; MEDINA VA

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Histamine regulates the growth and development of different types of tumors. Although the role of histamine H4 receptor (H4R) in immune cells is extensively investigated, its immunomodulatory function in cancer is completely unknown. This study aimed to investigate the role of H4R in antitumor immunity in a model of triple negative breast cancer (TNBC). We evaluated growth parameters, histological characteristics of tumors and the composition of tumor, splenic and tumor draining lymph nodes (TDLN) immune subsets in a syngeneic model TNBC developed orthotopically with 4T1 cells in H4R knockout (H4R-KO) and wild-type (WT) mice.Mice lacking H4R show reduced tumor size and weight (1.6±0.2 g vs. 0.9±0.1 g, P=0.003) and decreased number of lung metastases. Tumors of H4R-KO mice exhibit a more differentiated histopathological pattern (grade 2) compared to WT mice (grade 3, highly aggressive potential) and display a significant decrease in the mitotic index and angiogenesis. H4R-deficency is associated with a decrease in the percentage of CD4+ tumor infiltrating T cells (p