期刊
INTERNATIONAL JOURNAL OF CANCER
卷 152, 期 8, 页码 1698-1706出版社
WILEY
DOI: 10.1002/ijc.34389
关键词
metabolic dysfunction; NK cells; tumor immunology; tumor microenvironment
类别
This study highlights the importance of metabolic interactions between NK cells and the tumor microenvironment and proposes metabolic dysfunction as a major mechanism behind NK cell failure in cancer treatment. The results show that IL15 plays an unprecedented role in the metabolic reprogramming of NK cells, enhancing their antitumor functions.
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.
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