Treatment of glioblastoma with immunogenic method

Background: GBM is one of the most comprehensive types ofcancer characterized from a genomic point of view, leading tothe identification of groups of tumors defined by transcriptionalprofiles (pre-neural, neural, classical and mesenchymal).Materials and Methods: The vast majority over۸۰% of the humangenome is transcribed into RNA. However, only ۲% ofRNA is translated into proteins. Consequently, the vast majorityof cellular RNAs are noncoding RNAs (ncRNAs). small ncRNAs(microRNAs; ۱۷–۲۲ nucleotides) and long ncRNAs (lncRNAs over ۲۰۰ nucleotides). miRNAs are frequently deregulatedin human cancers via genetic, epigenetic, transcriptional,and processing mechanisms Deregulation of miRNA expressionhas been associated with cancer initiation, progression,and metastasis.By targeting the mRNAs of oncogenes or tumor suppressors,miRNAs can act as tumor suppressors or oncogenes, respectively.miRNAs regulate all aspects of cancer biology includingcell cycle, proliferation, death, apoptosis, migration, invasion,metastasis, angiogenesis, tumor microenvironment, tumor immunology.Results: exhausted T cells in the tumor microenvironmentshow overexpressed inhibitory receptors, decreased effectorcytokine production and cytolytic activity, leading to the failureof cancer elimination.T-cell exhaustion is a state of T-cell dysfunction in chronic environment,exhausted T cells express high levels of inhibitoryreceptors, including programmed cell death protein ۱ (PD-۱),lymphocyte activation gene ۳ protein (LAG-۳), T-cell immunoglobulindomain and mucin domain protein ۳ (TIM-۳), cytotoxicT lymphocyte antigen-۴ (CTLA-۴), band T lymphocyteattenuator (BTLA) and T-cell immunoglobulin.Conclusion: Chimeric antigen receptors (CARs) are engineeredfusion proteins constructed from antigen recognition, signaling,and costimulatory domains that can be expressed in cytotoxicT cells with the purpose of reprograming the T cells to specificallytarget tumor cells. CAR T-cell therapy uses gene transfertechnology to reprogram a patient's own T cells to stably expressCARs, thereby combining the specificity of an antibodywith the potent cytotoxic and memory functions of a T cell