Tumor-antigens and immune landscapes identification for prostate adenocarcinoma mRNA vaccine

Mol Cancer. 2021 Dec 6;20(1):160. doi: 10.1186/s12943-021-01452-1.

Abstract

Prostate adenocarcinoma (PRAD) is a leading cause of death among men. Messenger ribonucleic acid (mRNA) vaccine presents an attractive approach to achieve satisfactory outcomes; however, tumor antigen screening and vaccination candidates show a bottleneck in this field. We aimed to investigate the tumor antigens for mRNA vaccine development and immune subtypes for choosing appropriate patients for vaccination. We identified eight overexpressed and mutated tumor antigens with poor prognostic value of PRAD, including KLHL17, CPT1B, IQGAP3, LIME1, YJEFN3, KIAA1529, MSH5 and CELSR3. The correlation of those genes with antigen-presenting immune cells were assessed. We further identified three immune subtypes of PRAD (PRAD immune subtype [PIS] 1-3) with distinct clinical, molecular, and cellular characteristics. PIS1 showed better survival and immune cell infiltration, nevertheless, PIS2 and PIS3 showed cold tumor features with poorer prognosis and higher tumor genomic instability. Moreover, these immune subtypes presented distinguished association with immune checkpoints, immunogenic cell death modulators, and prognostic factors of PRAD. Furthermore, immune landscape characterization unraveled the immune heterogeneity among patients with PRAD. To summarize, our study suggests KLHL17, CPT1B, IQGAP3, LIME1, YJEFN3, KIAA1529, MSH5 and CELSR3 are potential antigens for PRAD mRNA vaccine development, and patients in the PIS2 and PIS3 groups are more suitable for vaccination.

Keywords: Immune landscape; Immune subtypes; Immunotherapy; Prostate adenocarcinoma; Tumor antigens; mRNA vaccine.

Publication types

  • Letter
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy
  • Antigens, Neoplasm / immunology*
  • Biomarkers, Tumor
  • Cancer Vaccines / immunology*
  • Cancer Vaccines / therapeutic use
  • Computational Biology / methods
  • Epitope Mapping
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Humans
  • Male
  • Prostatic Neoplasms / immunology*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / therapy
  • Reproducibility of Results
  • Transcriptome
  • Vaccines, Synthetic / immunology*
  • Vaccines, Synthetic / therapeutic use
  • mRNA Vaccines / immunology*
  • mRNA Vaccines / therapeutic use

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Cancer Vaccines
  • Vaccines, Synthetic
  • mRNA Vaccines