ANTITUMORAL AND IMMUNOMODULATORY ROLE OF HISTAMINE IN BREAST CANCER

MASSARI NA; HERRERO DUCLOUX, MA; NICOUD, MB; TÁQUEZ DELGADO, MA; MARTINEL LAMAS DJ; STERLE HA; FORMOSO K; MEDINA VA

Mar del Plata

Congreso; Reunión Conjunta SAIC SAI SAFIS 2018; 2018

It is well known that histamine is a key regulator of immune cell functionsand it also modulates cancer cell proliferation. The aim of thiswork was to investigate the effect of histamine and its H4 receptor(H4R) agonist (JNJ28610244) on tumour growth and in the immunetumour microenvironment as a whole, in a triple negative breast cancer(TNBC) syngeneic model developed in immunocompetent mice.Tumours of the TNBC cell line 4T1 were established in Balb/c mice.Treatments employed: histamine (1 or 5 mg/kg) and JNJ28610244(1 or 5 mg kg). Results show that histamine treatment (5 mg/kg)reduces tumour growth more effectively than JNJ28610244. Histaminebut not the agonist increases tumour apoptosis and it reducesthe number of intratumoural vessels. Histamine also reduces immunosuppressionthrough the modulation of the tumour microenvironment,as it increases the tumour secretion of IFN gamma andreduces the number of T regulatory (Treg) lymphocytes in lymphnodes and spleen.A lower concentration (1 mg/kg) of JNJ28610244 reduces tumoursize while no immunomodulatory effects are observed in the immunecell subsets studied. In contrast, a higher concentration (5 mg/kg) isnot able to decrease tumour growth probably because of the immunosuppressiveeffect produced in the tumour microenvironment,showing increased levels of interleukin (IL)-10 and decreased levelsof IFNγ in tumours and increased infiltrating Treg cells in tumourdraining lymph nodes. These results highlight the critical interplaybetween tumour cells and host immune response that determine theclinical therapeutic outcomes and suggest that histamine is a keypleiotropic mediator with therapeutic benefits in TNBC.