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22.07.2020 | Original Article

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

verfasst von: Melisa B. Nicoud, Mónica A. Táquez Delgado, María de la Paz Sarasola, Agustina Vidal, Daniela Speisky, Graciela A. Cremaschi, Helena A. Sterle, Vanina A. Medina

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 1/2021

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Abstract

Background

The histamine H4 receptor (H4R) is preferentially expressed in immune cells and is a potential therapeutic target for inflammatory and autoimmune diseases. This study aimed at further exploring the role of H4R in the immunobiology of breast cancer.

Methods

We used wild type (WT) and H4R deficient mice (KO) to evaluate whether H4R genotypes show a different distribution of T cell subsets in spleens, tumours and tumour draining lymph nodes (TDLN) in a syngeneic ErbB2-positive breast 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 compared to WT ones. At day 21 post-inoculation (p.i.) of cells, despite no significant changes in the tumour weight, TDLN from KO mice showed a significantly increased proportion of CD8⁺ T cells compared to WT mice. At day 38 p.i. of cells a reduced tumour weight was evident in KO mice. This was accompanied by a decreased proportion of CD4⁺CD25⁺FoxP3⁺ regulatory T 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 immunosuppressive milieu. Results suggest that H4R could be explored as an immunotherapeutic target with potential benefit in combination with immunotherapy. Further preclinical and clinical studies are necessary to confirm this hypothesis.

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Titel: Impact of histamine H4 receptor deficiency on the modulation of T cells in a murine breast cancer model
verfasst von: Melisa B. Nicoud
Mónica A. Táquez Delgado
María de la Paz Sarasola
Agustina Vidal
Daniela Speisky
Graciela A. Cremaschi
Helena A. Sterle
Vanina A. Medina
Publikationsdatum: 22.07.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 1/2021
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-020-02672-y

Springer Medizin

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