ABSTRACT
Vaccination, for centuries, has been a potent preventive technique to treat morbidities. The messenger RNA (mRNA) vaccine technology is an innovative biomedical approach utilized in developing antigen-specific vaccines that can generate adaptive immune responses, triggering both humoral and cellular immunity to enhance the body's defense against specific infections. This review provides a comprehensive, comparative analysis of mRNA vaccine technology and conventional vaccines by focusing on the structures, components, and classifications. An exploratory analysis of the similarities and differences between mRNA vaccine technology and live-attenuated vaccines highlights the mechanisms by which mRNA vaccines elicit immune responses. This review extensively discusses the production, stability, synthesis, and delivery processes associated with mRNA vaccines, showcasing the advancements and technological superiority of this approach over conventional vaccine technologies. Additionally, the potential of mRNA vaccine technology as a potent alternative for the development of vaccine candidates targeting HIV and cancer is examined.
ABSTRACT
Triple-negative breast cancer (TNBC), characterized by a deficiency in estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor2 (HER2), is among the most lethal subtypes of breast cancer (BC). Nevertheless, the molecular determinants that contribute to its malignant phenotypes such as tumor heterogeneity and therapy resistance, remain elusive. In this study, we sought to identify the stemness-associated genes involved in TNBC progression. Using bioinformatics approaches, we found 55 up- and 9 downregulated genes in TNBC. Out of the 55 upregulated genes, a 5 gene-signature (CDK1, EZH2, CCNB1, CCNA2, and AURKA) involved in cell regeneration was positively correlated with the status of tumor hypoxia and clustered with stemness-associated genes, as recognized by Parametric Gene Set Enrichment Analysis (PGSEA). Enhanced infiltration of immunosuppressive cells was also positively correlated with the expression of these five genes. Moreover, our experiments showed that depletion of the transcriptional co-factor nucleus accumbens-associated protein 1 (NAC1), which is highly expressed in TNBC, reduced the expression of these genes. Thus, the five genes signature identified by this study warrants further exploration as a potential new biomarker of TNBC heterogeneity/stemness characterized by high hypoxia, stemness enrichment, and immune-suppressive tumor microenvironment.
ABSTRACT
The upregulation of co-inhibitory checkpoint receptors/ligands that inactivate antitumor T-cells, the enhancement of Tregs-mediated trogocytosis that contribute delayed maturation of antigen presenting cell (APC), and the high Tregs/CD+8 ratio that maintained low threshold of CD+8 cells in the tumor microenvironment (TME); all represent the nuances in the immune evasive strategies of pancreatic ductal adenocarcinoma (PDAC). PDAC is the most aggressive type of pancreatic cancers characterized by poor prognosis and extremely low survivability. Over the years, fraternity of scientists have developed therapeutic agents that can bolster the capacity of the antitumor immunity, usually via the inhibition of immune checkpoints. While this immune checkpoint inhibition therapy represents one major jab from immunity to PDAC, this cancer remains highly resistant due to the acme of desmoplasia in its TME. In this review, we discuss the mechanisms of various checkpoint receptors/ligands axes that are relevant to the fitness of PDAC in its oncogenic ring. These checkpoints include PD-1, CTLA-4, ICOS, TIM-3, TIGIT, BTLA, BTN3A, and VISTA. In addition, we provided evidences that are relevant to the understanding of immune checkpoint inhibition, with extensive outline of immune checkpoint inhibitors that are critical to the treatment of PDAC. Finally, we discuss recently known intricacies of PDAC-mediated immunosuppression, and current advances in treatment options. Having realized that the overall scenario between PDAC and antitumor immunity is like the throwing of jabs in a ring, we therefore discuss future directions and prospect that can knock out PDAC in favor of immunity and humanity.
