Asymmetric Dimethylarginine Disrupts Tumor Antigen Presentation in Breast Cancer

Asymmetric dimethylarginine (ADMA), an endogenous methylated amino acid, has been implicated in tumor progression; however, its influence on tumor immunity, particularly dendritic cell (DC) function and antigen presentation, remains unclear. In this study, we examined the effects of ADMA on tumor antigen uptake, processing, and presentation in DCs using the murine dendritic cell line DC2.4 as a model. Our results reveal that ADMA treatment significantly reduces the phagocytic uptake of tumor antigens derived from EO771 and Py230 breast cancer cell lysates. Additionally, ADMA exposure leads to a marked downregulation of key genes involved in antigen processing and presentation, including <i>MHC I</i>, <i>MHC II</i>, <i>TAP1</i>, <i>TAP2</i>, <i>ERp57</i>, and <i>CD80</i>. This suppression at the transcriptional level corresponds with decreased surface protein expression of MHC I, MHC II, and CD80, as confirmed by flow cytometry. Furthermore, ADMA-treated DC2.4 cells exhibit impaired tumor antigen presentation on their surface. Consequently, these functional impairments result in a diminished capacity to activate CD4⁺ T cells, as evidenced by a 41.18% decrease in CD25 expression and a 30.28% reduction in IFN-γ secretion. Similarly, CD8⁺ T cell activation is compromised, as indicated by a 32.26% decrease in IFN-γ production, although CD25 expression remains unaffected. Collectively, our findings identify ADMA as a potential immunosuppressive factor that disrupts antigen uptake, processing, and presentation in DCs, thereby modulating T cell activation. These insights suggest a potential mechanism through which ADMA may contribute to immune evasion within the tumor microenvironment.