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

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..

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:70

Enthalten in:

Cancer immunology immunotherapy - 70(2020), 1 vom: 22. Juli, Seite 233-244

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext [lizenzpflichtig]

BKL:

44.81$jOnkologie

44.45$jImmunologie

Themen:

Antitumour immunity
Breast cancer
Histamine H4 receptor
T regulatory cells

RVK:

RVK Klassifikation

Anmerkungen:

© Springer-Verlag GmbH Germany, part of Springer Nature 2020

doi:

10.1007/s00262-020-02672-y

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

OLC2123002410

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