Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 23, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/ijms23010164
Keywords
NK cell; immunotherapy; solid tumor; immune checkpoint inhibitors; BiKE; TriKE; CAR-NK; NK cell therapy
Funding
- GuangdongHong KongMacao Joint Labs Program from Guangdong Science and Technology [2019B121205005]
- Innovation and Technology Fund of Hong Kong [ITS/138/17]
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This article reviews the challenges encountered by NK cells in the solid tumor microenvironment and the therapeutic approaches to overcome these limitations. It also outlines the recent preclinical advances and the latest clinical outcomes of NK-based immunotherapies for solid tumors, as well as promising strategies to optimize current NK-targeted immunotherapies.
Natural killer (NK) cell is a powerful malignant cells killer, providing rapid immune responses via direct cytotoxicity without the need of antigen processing and presentation. It plays an essential role in preventing early tumor, metastasis and minimal residual disease. Although adoptive NK therapies achieved great success in clinical trials against hematologic malignancies, their accumulation, activation, cytotoxic and immunoregulatory functions are severely impaired in the immunosuppressive microenvironment of solid tumors. Now with better understandings of the tumor evasive mechanisms from NK-mediated immunosurveillance, immunotherapies targeting the key molecules for NK cell dysfunction and exhaustion have been developed and tested in both preclinical and clinical studies. In this review, we introduce the challenges that NK cells encountered in solid tumor microenvironment (TME) and the therapeutic approaches to overcome these limitations, followed by an outline of the recent preclinical advances and the latest clinical outcomes of NK-based immunotherapies, as well as promising strategies to optimize current NK-targeted immunotherapies for solid tumors.
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