Identification of tumor antigens and immune subtypes of cholangiocarcinoma for mRNA vaccine development

Abstract Background The mRNA-based cancer vaccine has been considered a promising strategy and the next hotspot in cancer immunotherapy. However, its application on cholangiocarcinoma remains largely uncharacterized. This study aimed to identify potential antigens of cholangiocarcinoma for development of anti-cholangiocarcinoma mRNA vaccine, and determine immune subtypes of cholangiocarcinoma for selection of suitable patients from an extremely heterogeneous population. Methods Gene expression profiles and corresponding clinical information were collected from GEO and TCGA, respectively. cBioPortal was used to visualize and compare genetic alterations. GEPIA2 was used to calculate the prognostic index of the selected antigens. TIMER was used to visualize the correlation between the infiltration of antigen-presenting cells and the expression of the identified antigens. Consensus clustering analysis was performed to identify the immune subtypes. Graph learning-based dimensionality reduction analysis was conducted to visualize the immune landscape of cholangiocarcinoma. Results Three tumor antigens, such as CD247, FCGR1A, and TRRAP, correlated with superior prognoses and infiltration of antigen-presenting cells were identified in cholangiocarcinoma. Cholangiocarcinoma patients were stratified into two immune subtypes characterized by differential molecular, cellular and clinical features. Patients with the IS1 tumor had immune “hot” and immunosuppressive phenotype, whereas those with the IS2 tumor had immune “cold” phenotype. Interestingly, patients with the IS2 tumor had a superior survival than those with the IS1 tumor. Furthermore, distinct expression of immune checkpoints and immunogenic cell death modulators was observed between different immune subtype tumors. Finally, the immune landscape of cholangiocarcinoma revealed immune cell components in individual patient. Conclusions CD247, FCGR1A, and TRRAP are potential antigens for mRNA vaccine development against cholangiocarcinoma, specifically for patients with IS2 tumors. Therefore, this study provides a theoretical basis for the anti-cholangiocarcinoma mRNA vaccine and defines suitable patients for vaccination.