Overexpression of LLT1 (OCIL, CLEC2D) on prostate cancer cells inhibits NK cell-mediated killing through LLT1-NKRP1A (CD161) interaction
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Authors
ORCID
0000-0003-0518-4120 (Chaudhary, Pankaj)
0000-0002-0266-6020 (Vishwanatha, Jamboor K.)
0000-0001-8137-0895 (Mathew, Porunelloor A.)
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Journal ISSN
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Abstract
Prostate 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.
Description
Keywords
LLT1-NKRP1A interaction
NK cells
Nkrp1a (cd161)
prostate cancer
Antibodies, Blocking / immunology
Antibodies, Blocking / pharmacology
Cell Line, Tumor
Cytotoxicity, Immunologic / drug effects
Cytotoxicity, Immunologic / genetics
Cytotoxicity, Immunologic / immunology
Gene Expression Regulation, Neoplastic / immunology
Humans
Jurkat Cells
Killer Cells, Natural / immunology
Killer Cells, Natural / metabolism
Lectins, C-Type / genetics
Lectins, C-Type / immunology
Lectins, C-Type / metabolism
Male
NK Cell Lectin-Like Receptor Subfamily B / genetics
NK Cell Lectin-Like Receptor Subfamily B / immunology
NK Cell Lectin-Like Receptor Subfamily B / metabolism
Prostatic Neoplasms / genetics
Prostatic Neoplasms / immunology
Prostatic Neoplasms / metabolism
Protein Binding / drug effects
Receptors, Cell Surface / genetics
Receptors, Cell Surface / immunology
Receptors, Cell Surface / metabolism