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Tytuł pozycji:

Iron Supplementation Interferes With Immune Therapy of Murine Mammary Carcinoma by Inhibiting Anti-Tumor T Cell Function

Tytuł:
Iron Supplementation Interferes With Immune Therapy of Murine Mammary Carcinoma by Inhibiting Anti-Tumor T Cell Function
Autorzy:
Piotr Tymoszuk
Manfred Nairz
Natascha Brigo
Verena Petzer
Simon Heeke
Brigitte Kircher
Natascha Hermann-Kleiter
Victoria Klepsch
Igor Theurl
Günter Weiss
Christa Pfeifhofer-Obermair
Temat:
T cell
immunotherapy
cancer prognosis
iron
immune checkpoint
mammary carcinoma
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Źródło:
Frontiers in Oncology, Vol 10 (2020)
Wydawca:
Frontiers Media S.A., 2020.
Rok publikacji:
2020
Kolekcja:
LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Typ dokumentu:
article
Opis pliku:
electronic resource
Język:
English
ISSN:
2234-943X
Relacje:
https://www.frontiersin.org/articles/10.3389/fonc.2020.584477/full; https://doaj.org/toc/2234-943X
DOI:
10.3389/fonc.2020.584477
Dostęp URL:
https://doaj.org/article/758e71acede04078b495fde2040cc384  Link otwiera się w nowym oknie
Numer akcesji:
edsdoj.758e71acede04078b495fde2040cc384
Czasopismo naukowe
Iron is both, an essential compound for many metabolic processes, and iron deficiency can impact on the proliferation of cells including lymphocytes but also tumor cells. On the other hand, excess iron-catalyzed radical formation can induce cellular toxicity which has been previously demonstrated for T cells in hereditary iron overload. Despite these interconnections, little is known on the effects of clinically approved intravenous iron supplements for curing cancer-related anemia, on T cell differentiation, tumor proliferation, anti-tumor T cell responses and, of clinical importance, on efficacy of cancer immunotherapies. Herein, we analyzed the effects of intravenous iron supplementation on T cell function and on the effectiveness of anti-cancer chemotherapy with IL-2/doxorubicin or immunotherapy with checkpoint-inhibitor anti-PD-L1 in C57Bl/6N female mice with implanted E0771 mammary carcinomas. We found that iron application resulted to an increased availability of iron in the tumor microenvironment and stimulation of tumor growth. In parallel, iron application inhibited the activation, expansion and survival of cytotoxic CD8+ T cells and of CD4+ T helper cells type 1 and significantly reduced the efficacy of the investigated anti-cancer treatments. Our results indicate that iron administration has a tumor growth promoting effect and impairs anti-cancer responses of tumor infiltrating T lymphocytes along with a reduced efficacy of anti-cancer therapies. Iron supplementation in cancer patients, especially in those treated with immunotherapies in a curative setting, may be thus used cautiously and prospective studies have to clarify the impact of such intervention on the outcome of patients.

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