The MHC Class-I Transactivator NLRC5: Implications to Cancer Immunology and Potential Applications to Cancer Immunotherapy.

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.

Interventions to chronic prostatitis/Chronic pelvic pain syndrome treatment. Where are we standing and what's next?

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a frustrating syndrome. The pathogenesis and state of the art treatment of CP/CPPS are not known. A wide variety of therapies including anti-inflammatories, antibiotics, alpha-blockers, neuropathic pain modulators, and 5α-reductase inhibitors are in practice. These treatment strategies focus on alleviating symptoms in specific domains without treating root-cause and therapeutic outcome is far from satisfactory. We review the literature on current pharmacological treatments for CP/CPPS in detail and suggest future perspectives to modify the treatment strategies. We suggest that introducing novel treatment strategies such as gene editing, and Tregs expressing chimeric receptors may improve the treatment outcomes by inducing immune tolerance and controlling expression of pro-inflammatory cytokines.