Identification of novel tumor antigens and immune subtypes in breast cancer patients for mRNA vaccine development

Abstract

Background:Breast cancer has overtaken lung cancer as the world's most common malignancy. Despite the development of some mRNA vaccines, no satisfactory vaccination for breast cancer has entered clinical application. Methods:In this study, we used multiple analyses of expression datasets from public sources to find new possible tumor antigens for breast cancer and to hunt for potential treatment-sensitive patients. Results: We identified the antigens DST, ANO6, LAMA3, and NEDD9 as putative candidates. Furthermore, we found five predictive genes to identify specific patients inclined for vaccination, namely TRBC2, CD3D, CD27, CD3E, and TRBV28. Following that, we discovered three immunological subtypes of breast cancer, Cluster 1 and Cluster 3, which were recognized as "cold tumors" with minimal immune activity and were more likely to respond to vaccination. We uncovered that Cluster 1 and Cluster 3 could be further separated into two subgroups, each with distinct immune cell infiltration patterns, suggesting that vaccine responses could differ among these patients. The findings of our study lay theoretical foundation for the development of mRNA vaccine and provide new opportunities for personalized treatment.