Identification of tumor antigens and immune subtypes in lung squamous cell carcinoma for mRNA vaccine development

Abstract

Background: Cancer vaccines are therapies that activate the patient's own immune system by inoculating the patient with cancer-specific antigens to identify and clear cancer cells. Messenger ribonucleic acid (mRNA) vaccines have received much attention because of their ease of synthesis, relative affordability, and long-term safety, but have not been studied in lung squamous cell carcinoma (LUSC). Thus, the identification of tumor antigens is necessary to facilitate the development of mRNA vaccines for LUSC.Methods: Genes with significant copy number amplification, the presence of gene mutations in LUSC, and genes associated with survival were identified as potential tumor antigens. Subsequently, the genes significantly correlated with the level of infiltration of 3 antigen-presenting cells in LUSC were identified as LUSC tumor antigens. Unsupervised clustering and immune profiling analysis were used to identify potential suitable patients for mRNA vaccines. Lastly, drug sensitivity analysis was used to explore individualized treatment options for mRNA vaccines suitable and unsuitable patients.Results: In this study, among the highly mutated genes in LUSC, we found that bone morphogenetic protein 5 (BMP5) and claudin 5 (CLDN5) expression were positively correlated with antigen-presenting cell infiltration, which indicates that these 2 genes have potential for development as mRNA cancer vaccines.Further, the immune landscape analysis identified different immune subtypes. Our findings provide a reference for the development of treatment strategies and the prediction of treatment responsiveness.Conclusions: Overall, our study provides a new perspective on the development of mRNA vaccines for LUSC and highlights the importance of individualized therapy.

Progress and Challenges of Messenger RNA Vaccines in the Therapeutics of NSCLC

“…Those are primarily bioinformatics-based studies that used genomic data from publicly available datasets on genetic alterations for NSCLC [35]. Candidate targets are usually selected as those targets with a positive correlation with the filtration of immune cells and confirmed to induce APCs expression upon their appearance [35][36][37][38][39]. Researchers also seek to identify the expression patterns of NSCLC that might benefit from treatment with mRNA vaccination [35][36][37][38][39].…”

“…Another two genes with prognostic value, ZC3H12D and TXNDC5, were identified in a study by Zhao et al as potential targets for lung adenocarcinoma vaccines, based on their correlation with APC infiltration and tumor purity [38]. Finally, in a study that focused on lung squamous carcinoma, it was demonstrated that the expression patterns of the genes bone morphogenetic protein 5 (BMP5) and claudin 5 (CLDN5) were positively correlated with antigen-presenting cell infiltration, indicating their potential for development as mRNA cancer vaccines [39].…”