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

Abstract

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.

Identification of colon adenocarcinoma necroptosis subtypes and tumor antigens for the development of mRNA vaccines

“…As COAD develops and progresses, these antigens play an important role in their direct presentation to CD8 + T cells to induce an immune response upon lymphocyte infiltration. The potential of these candidate genes for mRNA vaccine development is supported by previous reports, although they have yet to be functionally validated [ 39 ]. This study is the first to screen for the potential antigens IL1B and BAX for the development of mRNA vaccines to treat patients with COAD.…”

“…mRNA vaccine development is a significant challenge. The tumors of different patients exhibit varying genetic and molecular characteristics, which complicates the development of vaccines targeting specific tumor antigens [ 39 ]. Immune suppressive factors within the tumor microenvironment may affect the efficacy of mRNA vaccines [ 48 ].…”

mRNA vaccine development and applications: A special focus on tumors (Review)

“…mRNA vaccines against colon adenocarcinoma are limited. A significant difficulty is sorting through the several vaccine candidates to identify possible mRNA vaccines that may be suitable for a specific type of cancer ( 145 ). Thrombospondin 2, follistatin like 3, troponin T1, biglycan, collagen triple helix repeat containing 1 and NADPH oxidase 4 are among the targeted antigens that Liu et al ( 139 ) identified as potential mRNA vaccine candidates.…”