Identifying tumor antigens and immuno-subtyping in colon adenocarcinoma to facilitate the development of mRNA vaccine.

The mRNA vaccine has provided a promising approach for cancer immunotherapies. However, only a few mRNA vaccines have been developed against colon adenocarcinoma (COAD). Screening potential targets for mRNA vaccines from numerous candidates is a substantial challenge. Considering the tumor heterogeneity, only a subset of patients might respond to vaccinations. This study was conducted to identify potential candidates for mRNA vaccines, and distinguish appropriate subgroups of COAD patients for vaccination. A total of five tumor antigens with prognostic values were identified, including IGF2BP3, DPCR1, HOXD10, TRIM7, and ZIC5. The COAD patients were stratified into five immune subtypes (IS1-IS5), according to consensus clustering analysis. Higher tumor mutation burden (TMB) was observed in IS1 and IS5 subtypes. The IS1 and IS5 subtypes have shown the baseline of immune-hot tumor microenvironment, while other subtypes displayed immune desert phenotype. Distinct expressions of immune checkpoints (ICPs)-related genes and immunogenic cell death (ICD) modulators were observed among five immune subtypes. Finally, the immune landscape was conducted to narrow the immune components for better personalized mRNA-based vaccination. The IFIT3, PARP9, TAP1, STAT1, and OAS2 were confirmed as hub genes, and COAD patients with higher expressions of these genes might be more appropriate for mRNA vaccination. In conclusion, the IGF2BP3, DPCR1, HOXD10, TRIM7, and ZIC5 were identified as potential candidates for developing mRNA vaccines against COAD, and patients in IS1 and IS5 subtypes might respond better to mRNA vaccination.

Cell deaths: Involvement in the pathogenesis and intervention therapy of COVID-19.

The current pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has dramatically influenced various aspects of the world. It is urgent to thoroughly study pathology and underlying mechanisms for developing effective strategies to prevent and treat this threatening disease. It is universally acknowledged that cell death and cell autophagy are essential and crucial to maintaining host homeostasis and participating in disease pathogenesis. At present, more than twenty different types of cell death have been discovered, some parts of which have been fully understood, whereas some of which need more investigation. Increasing studies have indicated that cell death and cell autophagy caused by coronavirus might play an important role in virus infection and pathogenicity. However, the knowledge of the interactions and related mechanisms of SARS-CoV-2 between cell death and cell autophagy lacks systematic elucidation. Therefore, in this review, we comprehensively delineate how SARS-CoV-2 manipulates diverse cell death (including apoptosis, necroptosis, pyroptosis, ferroptosis, and NETosis) and cell autophagy for itself benefits, which is simultaneously involved in the occurrence and progression of COVID-19, aiming to provide a reasonable basis for the existing interventions and further development of novel therapies.