The MHC Class-I Transactivator NLRC5: Implications to Cancer Immunology and Potential Applications to Cancer Immunotherapy |
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Authors: | Akhil Shukla Maryse Cloutier Madanraj Appiya Santharam Sheela Ramanathan Subburaj Ilangumaran |
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Affiliation: | 1.Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada; (A.S.); (M.C.); (M.A.S.); (S.R.);2.CRCHUS, Centre Hospitalier de l’Université de Sherbrooke, Sherbrooke, QC J1H5N4, Canada |
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Abstract: | The immune system constantly monitors the emergence of cancerous cells and eliminates them. CD8+ cytotoxic T lymphocytes (CTLs), which kill tumor cells and provide antitumor immunity, select their targets by recognizing tumor antigenic peptides presented by MHC class-I (MHC-I) molecules. Cancer cells circumvent immune surveillance using diverse strategies. A key mechanism of cancer immune evasion is downregulation of MHC-I and key proteins of the antigen processing and presentation machinery (APM). Even though impaired MHC-I expression in cancers is well-known, reversing the MHC-I defects remains the least advanced area of tumor immunology. The discoveries that NLRC5 is the key transcriptional activator of MHC-I and APM genes, and genetic lesions and epigenetic modifications of NLRC5 are the most common cause of MHC-I defects in cancers, have raised the hopes for restoring MHC-I expression. Here, we provide an overview of cancer immunity mediated by CD8+ T cells and the functions of NLRC5 in MHC-I antigen presentation pathways. We describe the impressive advances made in understanding the regulation of NLRC5 expression, the data supporting the antitumor functions of NLRC5 and a few reports that argue for a pro-tumorigenic role. Finally, we explore the possible avenues of exploiting NLRC5 for cancer immunotherapy. |
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Keywords: | NLRC5 MHC-I cancer immunotherapy |
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