“…The epigenetic regulation of Ciita by VPA is the suspected cause of the increased expression of Ciita in thymocytes due to demethylation after therapy with DCA–VPA. If this is the case, such an effect may be beneficial for cancer therapy, as epigenetic inhibition of Ciita in tumor cells may prevent the immune system from recognizing the tumor antigen and, thus, the anti-tumor immune response [ 126 ].…”
The research presents data from a preclinical study on the anti-inflammatory effects of a sodium dichloroacetate and sodium valproate combination (DCA–VPA). The 2-week treatment with a DCA 100 mg/kg/day and VPA 150 mg/kg/day combination solution in drinking water’s effects on the thymus weight, its cortex/medulla ratio, Hassall’s corpuscles (HCs) number in the thymus medulla, and the expression of inflammatory and immune-response-related genes in thymocytes of male Balb/c mice were studied. Two groups of mice aged 6–7 weeks were investigated: a control (n = 12) and a DCA–VPA-treated group (n = 12). The treatment did not affect the body weight gain (p > 0.05), the thymus weight (p > 0.05), the cortical/medulla ratio (p > 0.05), or the number of HCs (p > 0.05). Treatment significantly increased the Slc5a8 gene expression by 2.1-fold (p < 0.05). Gene sequence analysis revealed a significant effect on the expression of inflammation-related genes in thymocytes by significantly altering the expression of several genes related to the cytokine activity pathway, the inflammatory response pathway, and the Il17 signaling pathway in thymocytes. Data suggest that DCA–VPA exerts an anti-inflammatory effect by inhibiting the inflammatory mechanisms in the mouse thymocytes.
“…The epigenetic regulation of Ciita by VPA is the suspected cause of the increased expression of Ciita in thymocytes due to demethylation after therapy with DCA–VPA. If this is the case, such an effect may be beneficial for cancer therapy, as epigenetic inhibition of Ciita in tumor cells may prevent the immune system from recognizing the tumor antigen and, thus, the anti-tumor immune response [ 126 ].…”
The research presents data from a preclinical study on the anti-inflammatory effects of a sodium dichloroacetate and sodium valproate combination (DCA–VPA). The 2-week treatment with a DCA 100 mg/kg/day and VPA 150 mg/kg/day combination solution in drinking water’s effects on the thymus weight, its cortex/medulla ratio, Hassall’s corpuscles (HCs) number in the thymus medulla, and the expression of inflammatory and immune-response-related genes in thymocytes of male Balb/c mice were studied. Two groups of mice aged 6–7 weeks were investigated: a control (n = 12) and a DCA–VPA-treated group (n = 12). The treatment did not affect the body weight gain (p > 0.05), the thymus weight (p > 0.05), the cortical/medulla ratio (p > 0.05), or the number of HCs (p > 0.05). Treatment significantly increased the Slc5a8 gene expression by 2.1-fold (p < 0.05). Gene sequence analysis revealed a significant effect on the expression of inflammation-related genes in thymocytes by significantly altering the expression of several genes related to the cytokine activity pathway, the inflammatory response pathway, and the Il17 signaling pathway in thymocytes. Data suggest that DCA–VPA exerts an anti-inflammatory effect by inhibiting the inflammatory mechanisms in the mouse thymocytes.
“…As mentioned, mutations in the NF-κB pathway are rare, and have not been reported, except in some infection-related cancers and liquid malignancies. However, mutations upstream of NF-κB, or infection by viruses can disrupt the activity of this pathway and ultimately contribute to tumor progression [ 76 ].…”
Section: The Role Of Nf-κb In Cancer Progressionmentioning
Advances in cancer immunotherapy over the last decade have led to the development of several agents that affect immune checkpoints. Inhibitory receptors expressed on T cells that negatively regulate the immune response include cytotoxic T‑lymphocyte antigen 4 (CTLA4) and programmed cell death protein 1 (PD1), which have been studied more than similar receptors. Inhibition of these proteins and other immune checkpoints can stimulate the immune system to attack cancer cells, and prevent the tumor from escaping the immune response. However, the administration of anti-PD1 and anti-CTLA4 antibodies has been associated with adverse inflammatory responses similar to autoimmune diseases. The current review discussed the role of the NF-κB pathway as a tumor promoter, and how it can govern inflammatory responses and affect various immune checkpoints. More precise knowledge about the communication between immune checkpoints and NF-κB pathways could increase the effectiveness of immunotherapy and reduce the adverse effects of checkpoint inhibitor therapy.
Graphical abstract
“…In their comprehensive review, Forlani et al. delve into the complex world of the MHC class II transactivator (CIITA), a pivotal orchestrator in the gene expression of major histocompatibility complex class II (MHC-II), and a member of the heterogeneous NLR protein family [ 6 ]. While CIITA's well-established role revolves around the transcriptional regulation of MHC genes, it extends its influence over a constellation of more than 60 immunologically crucial genes, including the likes of IL-4 and IL-10 [ 7 ].…”
Section: Spotlightmentioning
confidence: 99%
“…However, involving CIITA opens up an exciting avenue wherein modified tumor cells can closely emulate physiological MHC-II expression, paving the way for innovative anti-tumor vaccination strategies [ Fig. 1 ] [ 6 ]. Fig.…”
Section: Spotlightmentioning
confidence: 99%
“…CIITA modified cancer cells are set up to express functional MHC class II molecules in a physiological fashion. Purified and selected tumor-specific peptides can then be used to craft a vaccine cocktail for therapeutic purposes [ 6 ]. …”
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