Identification of esophageal cancer tumor antigens and immune subtypes for guiding vaccine development

Highlight box

Key findings

• This study aimed to investigate the immunophenotype of esophageal cancer (ESCA) by assessing the patient’s immune defenses or autoimmune function and to identify potential tumor antigens and determine viable targets for vaccination based on the immune landscape.

What is known and what is new?

• The comprehensive analysis of The Cancer Genome Atlas (TCGA) data has consistently revealed the presence of three distinct immune subtypes. These subtypes serve as a foundation for understanding the complex interactions between tumors and the immune system. By identifying these subtypes, researchers have been able to construct a detailed immune landscape for TCGA samples, providing insights into how tumors interact with the immune response.

• Our comprehensive analysis has pinpointed six overexpressed and mutated tumor antigens that exhibit a strong correlation with both poor prognosis and the infiltration of antigen-presenting cells in ESCA. These antigens play a critical role in the immune response and tumor progression, making them potential targets for further investigation in therapeutic strategies.

What is the implication, and what should change now?

• This study’s findings suggest that BTN2A1, MICA, and HHLA2 display significant potential as antigens for the development of anti-ESCA messenger (mRNA) vaccines. The identification of three stable and reproducible immune subtypes specific to ESCA may prove essential in predicting the outcome of mRNA vaccines.

Abstract

Background: Esophageal cancer (ESCA) is a highly aggressive malignancy characterized by poor prognosis, primarily due to late diagnosis and limited treatment efficacy. Immunotherapies, such as vaccines, necessitate a more comprehensive understanding of the tumor immune microenvironment and tumor-specific antigens. The immune heterogeneity of ESCA, which is shaped by immune cell infiltration and antigen presentation, remains largely unexplored, particularly in terms of its interactions with autoimmune mechanisms. This study employs multi-omics analysis to profile the immunophenotype of ESCA, aiming to identify immune evasion mechanisms, tumor antigens, and autoimmune-related pathways. By elucidating these features, we seek to uncover potential targets for vaccine development and personalized immunotherapies, thereby improving therapeutic outcomes.

Methods: To screen for potential antigen genes, we examined the overexpressed and mutated genes specific to ESCA. Additionally, we employed Kaplan-Meier survival and Cox analysis to evaluate the prognostic relevance of these potential tumor antigens. To achieve data aggregation and construct a consistency matrix, we used consistency clustering. Subsequently, a graph learning-based dimensionality reduction method was implemented to clarify the immune subtypes. Furthermore, weighted gene coexpression network analysis (WGCNA) was used to cluster potential antigen genes and identify hub genes.

Results: Our analysis identified six overexpressed and mutated tumor antigens that were strongly associated with poor prognosis and antigen-presenting cell (APC) infiltration in ESCA. Analysis of The Cancer Genome Atlas (TCGA) data consistently identified three immune subtypes. These findings allowed for the construction of the immune landscape of TCGA samples based on the respective immune subtypes. The integration of immunogenomics analysis further allowed for the characterization of the immune microenvironment for each immune subtype. WGCNA successfully screened for three prognostic factors.

Conclusions: In our analysis, BTN2A1, MICA, and HHLA2 displayed significant potential as antigens for the development of anti-ESCA messenger RNA (mRNA) vaccines. The identification of three stable and reproducible immune subtypes specific to ESCA may prove essential in predicting the outcome of mRNA vaccines.

Keywords: Esophageal cancer (ESCA); immune subtype; survival analysis; mRNA vaccine