Identification of novel tumor antigens and immune subtypes in breast cancer patients for mRNA vaccine development
Introduction: Breast cancer has surpassed lung cancer to become the most prevalent malignant tumor worldwide. Although several mRNA vaccines have been developed, no ideal breast cancer vaccine has yet been applied clinically.
Objective: We sought to bridge fundamental tumor biology with translational vaccine development, ultimately providing a theoretical foundation for both breast cancer mRNA vaccines and individualized treatment approaches.
Methods: In this study, we performed integrated analyses using multiple publicly available expression datasets to identify novel potential tumor antigens for breast cancer and screen patient populations that may benefit from vaccination.
Results: We identified DST, ANO6, LAMA3, and NEDD9 as promising candidate antigens. In addition, we detected five predictive genes—TRBC2, CD3D, CD27, CD3E, and TRBV28—that can help recognize patients suitable for vaccine therapy. We further classified breast cancer into three immune subtypes, among which Cluster 1 and Cluster 3 exhibited low immune activity and were defined as “cold tumors,” which may be more responsive to vaccine treatment. Moreover, Cluster 1 and Cluster 3 could each be subdivided into two subgroups with distinct immune cell infiltration profiles, implying heterogeneous vaccine responses across these subgroups.
Conclusion: Collectively, our results provide a theoretical basis for the development of breast cancer mRNA vaccines and offer new insights into advancing personalized therapeutic strategies.
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