Immunomodulatory roles of histamine H4 receptor in breast cancer.

NOELIA MASSARI; HELENA STERLE; MONICA TÁQUEZ DELGADO; MELISA NICOUD

Capital Federal

Congreso; Reunión Conjunta de Sociedades de Biociencias - LXII Reunión Anual de la SAIC; 2017

Sociedad Argentina de Investigación Clínica

Histamine regulates the growth and development of differenttypes of tumors. Although the role of histamine H4 receptor (H4R)in immune cells is extensively investigated, its immunomodulatoryfunction in cancer is completely unknown. This study aimed to investigatethe role of H4R in antitumor immunity in a model of triplenegative 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 ina syngeneic model TNBC developed orthotopically with 4T1 cells inH4R knockout (H4R-KO) and wild-type (WT) mice.Mice lacking H4R show reduced tumor size and weight (1.6±0.2 gvs. 0.9±0.1 g, P=0.003) and decreased number of lung metastases.Tumors of H4R-KO mice exhibit a more differentiated histopathologicalpattern (grade 2) compared to WT mice (grade 3, highly aggressivepotential) and display a significant decrease in the mitotic indexand angiogenesis. H4R-deficency is associated with a decrease inthe percentage of CD4+ tumor infiltrating T cells (p