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Identifying novel tumor-related antigens and immune phenotypes for developing mRNA vaccines in lung adenocarcinoma

Bolun Zhou1, Ruochuan Zang1, Moyan Zhang1

  • 1Thoracic Surgery Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.

International Immunopharmacology
|May 3, 2022
PubMed

Insights

Messenger RNA (mRNA) vaccines show promise for lung adenocarcinoma (LUAD) immunotherapy. Researchers identified five antigens and found that patients with "cold" immune phenotypes (Groups S2&S3) are most suitable for mRNA vaccination.

Area of Science:

  • Oncology
  • Immunology
  • Vaccine Development

Background:

  • Messenger RNA (mRNA) vaccines represent a novel immunotherapy strategy for various cancers.
  • The efficacy of mRNA vaccines in lung adenocarcinoma (LUAD) patients is largely undetermined.
  • Identifying suitable patient subgroups and sufficient tumor-associated antigens is crucial for LUAD mRNA vaccine development.

Purpose of the Study:

  • To stratify lung adenocarcinoma (LUAD) patients based on immune profiles for potential mRNA vaccination.
  • To identify novel tumor-associated antigens suitable for LUAD mRNA vaccine development.
  • To explore the immune landscape of LUAD.

Main Methods:

  • Consensus clustering based on immune-related gene expression profiles to identify LUAD phenotypes.
  • Graph learning-based dimensionality reduction to analyze the LUAD immune landscape.
  • Screening for mutated and upregulated LUAD-related antigens correlated with immune infiltration and clinical outcomes.

Main Results:

  • Five mutated and upregulated LUAD-related antigens (CCNB1, KIAA0101, PBK, OIP5, PLEK2) were identified.
  • Three distinct immune phenotypes (Groups S1, S2, S3) were discovered across TCGA and GSE72094 cohorts.
  • Group S1 exhibited an "hot" immune phenotype with better prognosis, while Groups S2&S3 showed a "cold" immune phenotype associated with poorer prognosis.

Conclusions:

  • Lung adenocarcinoma (LUAD) patients display significant heterogeneity in their immune landscape.
  • Five novel cancer-related antigens were identified as potential targets for mRNA vaccines.
  • Patients with "cold" immune phenotypes (Groups S2&S3) are the most suitable candidates for mRNA vaccination in LUAD.
Keywords:
Immune landscapeImmunotherapyLung adenocarcinomaTumor microenvironmentmRNA vaccine

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