Cutting Edge: mTORC1 Inhibition in Metastatic Breast Cancer Patients Negatively Affects Peripheral NK Cell Maturation and Number.
J Immunol
; 206(10): 2265-2270, 2021 05 15.
Article
em En
| MEDLINE
| ID: mdl-33931486
ABSTRACT
NK cells are cytotoxic lymphocytes displaying strong antimetastatic activity. Mouse models and in vitro studies suggest a prominent role of the mechanistic target of rapamycin (mTOR) kinase in the control of NK cell homeostasis and antitumor functions. However, mTOR inhibitors are used as chemotherapies in several cancer settings. The impact of such treatments on patients' NK cells is unknown. We thus performed immunophenotyping of circulating NK cells from metastatic breast cancer patients treated with the mTOR inhibitor everolimus over a three-month period. Everolimus treatment resulted in inhibition of mTORC1 activity in peripheral NK cells, whereas mTORC2 activity was preserved. NK cell homeostasis was profoundly altered with a contraction of the NK cell pool and an overall decrease in their maturation. Phenotype and function of the remaining NK cell population was less affected. This is, to our knowledge, the first in vivo characterization of the role of mTOR in human NK cells.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Células Matadoras Naturais
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Transdução de Sinais
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Diferenciação Celular
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Proliferação de Células
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Everolimo
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Alvo Mecanístico do Complexo 1 de Rapamicina
/
Antineoplásicos
Tipo de estudo:
Clinical_trials
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
/
Aged80
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Female
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Humans
/
Middle aged
País/Região como assunto:
Europa
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article