Roles of NK Cell Receptors 2B4 (CD244), CS1 (CD319), and LLT1 (CLEC2D) in Cancer

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dc.creatorBuller, Casey W.
dc.creatorMathew, Porunelloor A.
dc.creatorMathew, Stephen O.
dc.creator.orcid0000-0001-5784-224X (Mathew, Stephen O.)
dc.creator.orcid0000-0001-8137-0895 (Mathew, Porunelloor A.)
dc.date.accessioned2022-10-14T16:48:28Z
dc.date.available2022-10-14T16:48:28Z
dc.date.issued2020-07-01
dc.description.abstractNatural killer (NK) cells play a pivotal role in the immune system, especially in the recognition and clearance of cancer cells and infected cells. Their effector function is controlled by a delicate balance between the activating and inhibitory signals. We have identified 2B4 (CD244, SLAMF4) and CS1 (CD319, SLAMF7) as NK cell receptors regulating NK cell cytotoxicity. Lectin-like transcript 1 (LLT1), a member of the C-type lectin-like domain family 2 (CLEC2D), induced IFN-g production but did not directly regulate cytolytic activity. Interestingly, LLT1 expressed on other cells acts as a ligand for an NK cell inhibitory receptor NKRP1A (CD161) and inhibits NK cytolytic function. Extensive research has been done on novel therapies that target these receptors to increase the effector function of NK cells. The 2B4 receptor is involved in the rejection of melanoma cells in mice. Empliciti, an FDA-approved monoclonal antibody, explicitly targets the CS1 receptor and enhances the NK cell cytotoxicity against multiple myeloma cells. Our studies revealed that LLT1 is expressed on prostate cancer and triple-negative breast cancer cells and allows them to evade NK-cell-mediated killing. In this review, we describe NK cell receptors 2B4, CS1, and LLT1 and their potential in targeting cancer cells for NK-cell-mediated immunotherapy. New cancer immunotherapies like chimeric antigen receptor T (CAR-T) and NK (CAR-NK) cells are showing great promise in the treatment of cancer, and CAR cells specific to these receptors would be an attractive therapeutic option.
dc.description.sponsorshipThis research received no external funding.
dc.identifier.citationBuller, C. W., Mathew, P. A., & Mathew, S. O. (2020). Roles of NK Cell Receptors 2B4 (CD244), CS1 (CD319), and LLT1 (CLEC2D) in Cancer. Cancers, 12(7), 1755. https://doi.org/10.3390/cancers12071755
dc.identifier.issn2072-6694
dc.identifier.issue7
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31869
dc.identifier.volume12
dc.publisherMDPI
dc.relation.urihttps://doi.org/10.3390/cancers12071755
dc.rights.holder© 2020 by the authors.
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceCancers
dc.subject2b4
dc.subjectCs1
dc.subjectLlt1
dc.subjectcancer
dc.subjectimmunotherapy
dc.subjectnatural killer (NK) cells
dc.titleRoles of NK Cell Receptors 2B4 (CD244), CS1 (CD319), and LLT1 (CLEC2D) in Cancer
dc.typeArticle
dc.type.materialtext

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