The tumor microenvironment drives NK cell metabolic dysfunction leading to impaired antitumor activity.

Autor: Tumino N; Immunology Research Area, Innate Lymphoid Cells Unit, Bambino Gesù Children's Hospital IRCCS, Rome, Italy., Nava Lauson CB; Immunometabolism and Cancer Immunotherapy Unit, IRCCS Istituto Europeo di Oncologia, Milan, Italy., Tiberti S; Immunometabolism and Cancer Immunotherapy Unit, IRCCS Istituto Europeo di Oncologia, Milan, Italy., Besi F; Tumor Immunology, Bambino Gesù Children's Hospital IRCCS, Rome, Italy., Martini S; UO Immunology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy., Fiore PF; Tumor Immunology, Bambino Gesù Children's Hospital IRCCS, Rome, Italy., Scodamaglia F; SC Pneumologia Ospedale Villa Scassi, ASL3 Genovese, Genoa, Italy., Mingari MC; UO Immunology, IRCCS Ospedale Policlinico San Martino, Genoa, Italy., Moretta L; Tumor Immunology, Bambino Gesù Children's Hospital IRCCS, Rome, Italy., Manzo T; Immunometabolism and Cancer Immunotherapy Unit, IRCCS Istituto Europeo di Oncologia, Milan, Italy., Vacca P; Immunology Research Area, Innate Lymphoid Cells Unit, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
Jazyk: angličtina
Zdroj: International journal of cancer [Int J Cancer] 2023 Apr 15; Vol. 152 (8), pp. 1698-1706. Date of Electronic Publication: 2022 Dec 16.
DOI: 10.1002/ijc.34389
Abstrakt: NK cells represent key players capable of driving antitumor immune responses. However, the potent immunosuppressive activity of the tumor microenvironment (TME) may impair their effector function. Here, we strengthen the importance of metabolic interactions between NK cells and TME and propose metabolic dysfunction as one of the major mechanisms behind NK failure in cancer treatment. In particular, we described that TME has a direct negative impact on NK cell function by disrupting their mitochondrial integrity and function in pediatric and adult patients with primary and metastatic cancer. Our results will help to design new strategies aimed at increasing the NK cell antitumor efficacy by their metabolic reprogramming. In this regard, we reveal an unprecedented role of IL15 in the metabolic reprogramming of NK cells enhancing their antitumor functions. IL15 prevents the inhibitory effect of soluble factors present in TME and restores both the metabolic characteristics and the effector function of NK cells inhibited by exposure to malignant pleural fluid. Thus, we propose here that IL15 may be exploited as a new strategy to metabolically reprogram NK cells with the aim of increasing the efficacy of NK-based immunotherapy in a wide range of currently refractory adult and pediatric solid tumors.
(© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)
Databáze: MEDLINE
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