Overexpression of LLT1 (OCIL, CLEC2D) on prostate cancer cells inhibits NK cell-mediated killing through LLT1-NKRP1A (CD161) interaction

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dc.creatorMathew, Stephen O.
dc.creatorChaudhary, Pankaj
dc.creatorPowers, Sheila B.
dc.creatorVishwanatha, Jamboor K.
dc.creatorMathew, Porunelloor A.
dc.creator.orcid0000-0001-5784-224X (Mathew, Stephen O.)
dc.creator.orcid0000-0003-0518-4120 (Chaudhary, Pankaj)
dc.creator.orcid0000-0002-0266-6020 (Vishwanatha, Jamboor K.)
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.issued2016-09-08
dc.description.abstractProstate cancer is the most common type of cancer diagnosed and the second leading cause of cancer-related death in American men. Natural Killer (NK) cells are the first line of defense against cancer and infections. NK cell function is regulated by a delicate balance between signals received through activating and inhibitory receptors. Previously, we identified Lectin-like transcript-1 (LLT1/OCIL/CLEC2D) as a counter-receptor for the NK cell inhibitory receptor NKRP1A (CD161). Interaction of LLT1 expressed on target cells with NKRP1A inhibits NK cell activation. In this study, we have found that LLT1 was overexpressed on prostate cancer cell lines (DU145, LNCaP, 22Rv1 and PC3) and in primary prostate cancer tissues both at the mRNA and protein level. We further showed that LLT1 is retained intracellularly in normal prostate cells with minimal cell surface expression. Blocking LLT1 interaction with NKRP1A by anti-LLT1 mAb on prostate cancer cells increased the NK-mediated cytotoxicity of prostate cancer cells. The results indicate that prostate cancer cells may evade immune attack by NK cells by expressing LLT1 to inhibit NK cell-mediated cytolytic activity through LLT1-NKRP1A interaction. Blocking LLT1-NKRP1A interaction will make prostate cancer cells susceptible to killing by NK cells and therefore may be a new therapeutic option for treatment of prostate cancer.
dc.description.sponsorshipThis work was supported by an intramural grant from University of North Texas Health Science Center, Fort Worth, TX to PAM.
dc.identifier.citationMathew, S. O., Chaudhary, P., Powers, S. B., Vishwanatha, J. K., & Mathew, P. A. (2016). Overexpression of LLT1 (OCIL, CLEC2D) on prostate cancer cells inhibits NK cell-mediated killing through LLT1-NKRP1A (CD161) interaction. Oncotarget, 7(42), 68650-68661. https://doi.org/10.18632/oncotarget.11896
dc.identifier.issn1949-2553
dc.identifier.issue42
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31868
dc.identifier.volume7
dc.publisherImpact Journals, LLC
dc.relation.urihttps://doi.org/10.18632/oncotarget.11896
dc.rights.holder© 2016 Mathew et al.
dc.rights.licenseAttribution 3.0 Unported (CC BY 3.0)
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/
dc.sourceOncotarget
dc.subjectLlt1
dc.subjectLLT1-NKRP1A interaction
dc.subjectNK cells
dc.subjectNkrp1a (cd161)
dc.subjectprostate cancer
dc.subject.meshAntibodies, Blocking / immunology
dc.subject.meshAntibodies, Blocking / pharmacology
dc.subject.meshCell Line, Tumor
dc.subject.meshCytotoxicity, Immunologic / drug effects
dc.subject.meshCytotoxicity, Immunologic / genetics
dc.subject.meshCytotoxicity, Immunologic / immunology
dc.subject.meshGene Expression Regulation, Neoplastic / immunology
dc.subject.meshHumans
dc.subject.meshJurkat Cells
dc.subject.meshKiller Cells, Natural / immunology
dc.subject.meshKiller Cells, Natural / metabolism
dc.subject.meshLectins, C-Type / genetics
dc.subject.meshLectins, C-Type / immunology
dc.subject.meshLectins, C-Type / metabolism
dc.subject.meshMale
dc.subject.meshNK Cell Lectin-Like Receptor Subfamily B / genetics
dc.subject.meshNK Cell Lectin-Like Receptor Subfamily B / immunology
dc.subject.meshNK Cell Lectin-Like Receptor Subfamily B / metabolism
dc.subject.meshProstatic Neoplasms / genetics
dc.subject.meshProstatic Neoplasms / immunology
dc.subject.meshProstatic Neoplasms / metabolism
dc.subject.meshProtein Binding / drug effects
dc.subject.meshReceptors, Cell Surface / genetics
dc.subject.meshReceptors, Cell Surface / immunology
dc.subject.meshReceptors, Cell Surface / metabolism
dc.titleOverexpression of LLT1 (OCIL, CLEC2D) on prostate cancer cells inhibits NK cell-mediated killing through LLT1-NKRP1A (CD161) interaction
dc.typeArticle
dc.type.materialtext

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