LACK OF HISTAMINE H4 RECEPTOR IN TUMOR MICROENVIRONMENT RESULTS IN REDUCED AGRESSIVENESS IN A MODEL OF BREAST CANCER. ROLE OF ANTITUMOR IMMUNITY

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

Amsterdam

Congreso; Joint meeting of the European and Japanese Histamine Research Societies; 2017

EUROPEAN HISTAMINE RESEARCH SOCIETY (EHRS), Japanese Histamine Research Society

The expression of histamine H4 receptor (H4R) and histamine-induced modulation of proliferation in different types of tumors has been previously reported. However, the role of H4R in tumor microenvironment, including immune cells, was not yet studied. Present work aims to investigate the effect on breast cancer development and progression of the lack of H4R in tumor microenvironment. We evaluated growth parameters, histological characteristics of tumors and the composition of tumoral immune subsets in a syngeneic model of breast cancer developed orthotopically with 4T1 cells in H4R knockout (H4R-KO) and wild-type (WT) mice.Mice lacking H4R show reduced tumor size and weight and exhibit a more differentiated histopathological pattern (grade 2) compared with WT mice (grade 3, highly aggressive potential). Tumors of H4R-KO mice display significant decrease in neutrophils (number of neutrophils per field: 3.2±0.9 vs. 9.0±2.1, P˂0.05) while non-significant differences in angiogenesis was observed. The lack of H4R is associated with an increase in the percentage of CD8+ (32.0±2.5 vs. 16.1±3.1, P˂0.05) and CD19+ (27.2±4.8 vs. 6.5±1.5, P˂0.01) tumor infiltrating lymphocytes and a decrease in CD4+ lymphocytes (11.9±3.4 vs. 19.4±1.2, P˂0.05). Similar differences in immune subsets are observed in the spleen. Finally, H4R-deficient mice showed non-significant changes in lung metastasis. These results suggest an interplay between H4R expressing cells in tumor microenvironment and cancer cells, which has implications in breast cancer progression