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

Ruo Qi Li; Wei Wang; Lei Yan; Li Ying Song; Xin Guan; Wei Zhang; Jing Lian

doi:10.3389/fonc.2022.973712

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

Front Oncol. 2022 Sep 26:12:973712. doi: 10.3389/fonc.2022.973712. eCollection 2022.

Authors

Ruo Qi Li^{1

2}, Wei Wang³, Lei Yan⁴, Li Ying Song⁵, Xin Guan⁶, Wei Zhang¹, Jing Lian¹

Affiliations

¹ Department of Pathology, Cancer Hospital Affiliated to Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China.
² General Surgery Department, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, China.
³ Department of Urologic Surgery, Shanxi Medical University Second Affiliated Hospital, Taiyuan, China.
⁴ Department of Orthopaedic Surgery, Shanxi Medical University Second Affiliated Hospital, Taiyuan, China.
⁵ Thyroid Surgery Department, First Hospital of Shanxi Medical University, Taiyuan, China.
⁶ Cardiovascular Department, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China.

Abstract

Background: Poor prognosis, resistance to chemotherapy, insensitivity to radiotherapy, and a high prevalence of adverse drug reactions remain urgent issues for breast cancer (BC) patients. Increased knowledge of tumor immunobiology and vaccine development suggests the possibility of cancer vaccination. Here, we investigated potential BC-associated antigens for the development of an anti-BC mRNA vaccine and populations suitable for mRNA vaccination.

Methods: Gene expression and clinical data were obtained from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC). The single-cell sequencing data were obtained from the Single Cell Portal platform. cBioPortal was used to visualize and compare genetic alterations. Correlations between immune cell infiltration and antigen expression were visualized with the Tumor Immune Estimation Resource (TIMER). Immune subtypes were identified by consensus clustering and analysis of immune infiltration. Biomarkers for the assessment of mRNA vaccination suitability were investigated.

Results: Three tumor-associated antigens, CD74, IRF1, and PSME2, that showed overexpression, amplification, and mutation and were linked with prognosis and immune cell infiltration, were identified. Single-cell sequencing analysis showed the expression of the three tumor-associated antigens in different cells of BC. Three immune subtypes were identified among BC patients, with Cluster B patients having a tumor microenvironment conducive to immunotherapy. These subtypes also showed different expression patterns of immune checkpoints, immune cell death-promoting genes, and response to immune checkpoint inhibitor (ICI) therapy. Thus, we identified five biomarkers that could be applied for assessing vaccination suitability and predicted drugs that would be appropriate for patients unsuited for vaccination.

Conclusions: Our findings suggest new directions for the development of mRNA vaccines against breast cancer.

Keywords: breast cancer; immune subtypes; mRNA vaccine; tumor antigen; tumor immune infiltration.