CONICET | Buscador de Institutos y Recursos Humanos

The histamine H4 receptor (H4R) is preferentially expressed in immunecells and is a potential therapeutic target for inflammatory andautoimmune diseases. This study aimed at further exploring the roleof H4R in the immunobiology of breast cancer.We used wild type (WT) and H4R deficient (H4R-KO) Balb/c miceto evaluate whether H4R genotypes show different distribution of Tcell subsets in spleens, tumours and tumour draining lymph nodes(TDLN) in a syngeneic ErbB2-positive breast cancer model developedorthotopically with LM3 cells and its impact on tumour growth.In addition, the migration capacity of TDLN cells from WT and KOanimals was analyzed.The presence of tumours had a differential impact on the distributionof T cells in TDLN from H4R-KO mice compared to WT ones. Atday 21 post inoculation (p.i.) of cells, despite no significant changesin the tumour weight, TDLN from H4R-KO mice showed a significantlyincreased proportion of CD8+ T cells compared to WT mice(P=0.0052). At day 38 p.i. of cells a reduced tumour weight was evidentin H4R-KO mice (P=0.0431). This was accompanied by a decreasedproportion of CD4+CD25+FoxP3+ regulatory T cells in TDLNof KO compared to WT mice (P=0.0104). In agreement with thetumour weights, the spleen weight was significantly reduced in tumour-bearing KO mice compared with WT counterparts (P=0.0280).Tumour-bearing KO mice showed a better survival compared to WTmice (P=0.0511). Furthermore, H4R deficient TDLN lymphocytesshowed impaired chemotaxis compared with WT mice (P=0.0054).We conclude that H4R-mediated mechanisms may modulate the immunetumour microenvironment, promoting an immunosuppressivemilieu. Results suggest that H4R could be explored as an immunotherapeutictarget with potential benefit in combination with immunotherapy.

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