UNDERSTANDING THE IMMUNOMODULATORY ROLE OF HISTAMINE H4 RECEPTOR IN BREAST CANCER. PERSPECTIVES TOWARDS AN IMMUNOTHERAPEUTIC APPROACH

NICOUD, MELISA B; OSPITAL, IGNACIO; TÁQUEZ DELGADO, MÓNICA A.; SPEISKY, DANIELA; VIDAL, AGUSTINA; STERLE, HA; CREMASCHI, G.A.; MEDINA, V.A.

hannover

Congreso; European Histamine Research Society 50th Annual Meeting; 2022

EUROPEAN HISTAMINE RESEARCH SOCIETY

The histamine H4 receptor (H4R) is a potential therapeutic target for inflammatory and autoimmune diseases. Recently, we have reported the participation of the H4R in the antitumour immunity in breast cancer. This study aimed at further exploring the role of H4R in the immunobiology of breast cancer.We developed a syngeneic breast cancer mouse model by orthotopic inoculation of 4T1 breast cancer cells in H4R knockout (H4R-KO) and wild-type (WT) mice. Treatments (mg kg-1): histamine (5), H4R agonist JNJ28610244 (1 and 5), and H4R antagonist JNJ7777120 (10).Histamine reduced tumor growth and increased tumor apoptosis, effects that were significantly enhanced in H4R-KO mice. Histamine reduced the percentage of tumor-infiltrating T helper (CD4+) cells and myeloid derived suppressor cells (MDSC), and increased the NK cells only in H4R-KO mice. Significant Spearman’s correlations between tumor weight and cytotoxic lymphocyte infiltration were detected only in histamine-treated H4R-KO mice (NK cells, r:-0.6364; CD8+ cells: r:-0.7697, P