Dataset Information

NKG2D Natural Killer Cell Receptor-A Short Description and Potential Clinical Applications.

ABSTRACT: Natural Killer (NK) cells are natural cytotoxic, effector cells of the innate immune system. They can recognize transformed or infected cells. NK cells are armed with a set of activating and inhibitory receptors which are able to bind to their ligands on target cells. The right balance between expression and activation of those receptors is fundamental for the proper functionality of NK cells. One of the best known activating receptors is NKG2D, a member of the CD94/NKG2 family. Due to a specific NKG2D binding with its eight different ligands, which are overexpressed in transformed, infected and stressed cells, NK cells are able to recognize and attack their targets. The NKG2D receptor has an enormous significance in various, autoimmune diseases, viral and bacterial infections as well as for transplantation outcomes and complications. This review focuses on the NKG2D receptor, the mechanism of its action, clinical relevance of its gene polymorphisms and a potential application in various clinical settings.

SUBMITTER: Siemaszko J

PROVIDER: S-EPMC8229527 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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NKG2D Natural Killer Cell Receptor-A Short Description and Potential Clinical Applications.

Siemaszko Jagoda J Marzec-Przyszlak Aleksandra A Bogunia-Kubik Katarzyna K

Cells 20210607 6

Natural Killer (NK) cells are natural cytotoxic, effector cells of the innate immune system. They can recognize transformed or infected cells. NK cells are armed with a set of activating and inhibitory receptors which are able to bind to their ligands on target cells. The right balance between expression and activation of those receptors is fundamental for the proper functionality of NK cells. One of the best known activating receptors is NKG2D, a member of the CD94/NKG2 family. Due to a specifi ...[more]

PMID: 34200375

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Project description:Sarcomas are malignancies of mesenchymal origin that occur in bone and soft tissues. Many are chemo- and radiotherapy resistant, thus conventional treatments fail to increase overall survival. Natural Killer (NK) cells exert anti-tumor activity upon detection of a complex array of tumor ligands, but this has not been thoroughly explored in the context of sarcoma immunotherapy. In this study, we investigated the NK cell receptor/ligand immune profile of primary human sarcoma explants. Analysis of tumors from 32 sarcoma patients identified the proliferative marker PCNA and DNAM-1 ligands CD112 and/or CD155 as commonly expressed antigens that could be efficiently targeted by genetically modified (GM) NK cells. Despite the strong expression of CD112 and CD155 on sarcoma cells, characterization of freshly dissociated sarcomas revealed a general decrease in tumor-infiltrating NK cells compared to the periphery, suggesting a defect in the endogenous NK cell response. We also applied a functional screening approach to identify relevant NK cell receptor/ligand interactions that induce efficient anti-tumor responses using a panel NK-92 cell lines GM to over-express 12 different activating receptors. Using GM NK-92 cells against primary sarcoma explants (n = 12) revealed that DNAM-1 over-expression on NK-92 cells led to efficient degranulation against all tested explants (n = 12). Additionally, NKG2D over-expression showed enhanced responses against 10 out of 12 explants. These results show that DNAM-1+ or NKG2D+ GM NK-92 cells may be an efficient approach in targeting sarcomas. The degranulation capacity of GM NK-92 cell lines was also tested against various established tumor cell lines, including neuroblastoma, Schwannoma, melanoma, myeloma, leukemia, prostate, pancreatic, colon, and lung cancer. Enhanced degranulation of DNAM-1+ or NKG2D+ GM NK-92 cells was observed against the majority of tumor cell lines tested. In conclusion, DNAM-1 or NKG2D over-expression elicited a dynamic increase in NK cell degranulation against all sarcoma explants and cancer cell lines tested, including those that failed to induce a notable response in WT NK-92 cells. These results support the broad therapeutic potential of DNAM-1+ or NKG2D+ GM NK-92 cells and GM human NK cells for the treatment of sarcomas and other malignancies.

Dataset Information

NKG2D Natural Killer Cell Receptor-A Short Description and Potential Clinical Applications.

Publications

NKG2D Natural Killer Cell Receptor-A Short Description and Potential Clinical Applications.

Similar Datasets

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