Impact of histamine H4 receptor deficiency on the modulation of T cells in a murine breast cancer model

NICOUD, MELISA B.; TÁQUEZ DELGADO, MÓNICA A.; SARASOLA, MARÍA DE LA PAZ; VIDAL, AGUSTINA; SPEISKY, DANIELA; CREMASCHI, GRACIELA A.; STERLE, HELENA A.; MEDINA, VANINA A.

CANCER IMMUNOLOGY IMMUNOTHERAPY

SPRINGER

Año: 2020

0340-7004

AbstractBackground The histamine H4 receptor (H4R) is preferentially expressed in immune cells and is a potential therapeutictarget for inflammatory and autoimmune diseases. This study aimed at further exploring the role of H4R in the immunobiologyof breast cancer.Methods We used wild type (WT) and H4R deficient mice (KO) to evaluate whether H4R genotypes show a differentdistribution of T cell subsets in spleens, tumours and tumour draining lymph nodes (TDLN) in a syngeneic ErbB2-positivebreast cancer model developed orthotopically with LM3 cells and its impact on tumour growth.Results The presence of tumours had a differential impact on the distribution of T cells in TDLN from KO mice comparedto WT ones. At day 21 post-inoculation (p.i.) of cells, despite no significant changes in the tumour weight, TDLN from KOmice showed a significantly increased proportion of CD8+T cells compared to WT mice. At day 38 p.i. of cells a reducedtumour weight was evident in KO mice. This was accompanied by a decreased proportion of CD4+CD25+FoxP3+ regulatoryT cells in TDLN of KO compared to WT mice. Tumour-bearing KO mice showed a better survival compared to WT mice.Conclusions H4R-mediated mechanisms may modulate the immune tumour microenvironment, promoting an immunosuppressivemilieu. Results suggest that H4R could be explored as an immunotherapeutic target with potential benefit in combinationwith immunotherapy. Further preclinical and clinical studies are necessary to confirm this hypothesis.