Identification of Tumor Antigens and Immune Subtypes in Lung Adenocarcinoma for mRNA Vaccine Development.

Ran Xu,Tong Lu,Linyou Zhang,Jiaying Zhao,Jun Wang,Bo Peng

doi:10.3389/fcell.2022.815596

Abstract

Cancer vaccines are emerging as a viable strategy for cancer treatment. In the current study, we screened for genes associated with the prognosis of patients with lung adenocarcinoma and positively correlated with antigen-presenting cell infiltration and identified KLRG1 and CBFA2T3 as potential tumor antigens for mRNA vaccines in lung adenocarcinoma (LUAD). Further analyses of immune subtypes revealed that patients with early-stage LUAD, high immune cell infiltration, high immune checkpoint expression, and low tumor mutation burden might benefit from mRNA vaccination. Moreover, we identified four biomarkers that can be used to assess mRNA vaccination suitability. We also identified potentially sensitive anti-cancer drugs for populations not suitable for vaccination by means of anti-cancer drug susceptibility prediction. Overall, we provided a new perspective for mRNA vaccine treatment strategies for LUAD and emphasized the importance of precise and personalized treatments.

Highlights

Lung cancer is the leading malignant disease death cause (Siegel et al, 2021) with a 5-years survival rate of 4–17% (Hirsch et al, 2017)
We considered genes affected by regions with significant chromosomal amplification and/or deletion as potential mRNA vaccine targets (Figures 1A,B)
We performed a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the copy number variant genes. Results showed that these genes were involved in the regulation of different cancer and immune-related pathways, demonstrating that these genes could be used as potential targets for cancer mRNA vaccines (Figure 1D)

Summary

Introduction

Lung cancer is the leading malignant disease death cause (Siegel et al, 2021) with a 5-years survival rate of 4–17% (Hirsch et al, 2017). Lung adenocarcinoma (LUAD) is the most common lung cancer pathological subtype and great progress has been made recently regarding individualized and precise treatments. Surgery is the primary treatment for early-stage LUAD but surgical opportunities are often missed in asymptomatic patients (Tanoue et al, 2015; Abbas 2018). Alternatives are required for those lung cancer patients that cannot undergo surgery. In these cases, other important treatment strategies can be used, such as targeted therapy (e.g., targeting EGFR mutations) and immunotherapy (Mayekar and Bivona 2017; Osmani et al, 2018). A new strategy for the precise treatment of LUAD needs to be developed

Methods

Results

Conclusion