Visiting Translocons Sec Roles in Antigen Presentation in Breast Cancer

Background: Translocons Sec61, Sec62, and Sec22B occupy a central yet underappreciated position in the regulation of antigen cross-presentation. Rather than serving redundant roles, each contributes a distinct function within endoplasmic reticulum (ER)-associated antigen processing. Sec61 primarily facilitates the translocation of internalized antigens into the cytosol for proteasomal processing, whereas Sec62 enables the selective reentry of processed peptides into the endoplasmic reticulum through mechanisms that can bypass canonical transporter associated with antigen processing (TAP) dependency. In parallel, Sec22B governs ER–phagosome fusion and vesicular trafficking, thereby shaping the spatial and temporal organization required for efficient peptide loading and major histocompatibility complex (MHC)-class I transport. In this review, we synthesize emerging evidence to argue that Sec translocons represent overlooked determinants in antigen presentation and may hold therapeutic relevance in breast cancer. Methods: Parallel inquiries in the PubMed database were performed with a query of Sec breast cancer. Subsequent assessments were manually conducted considering the relevance of the papers to our area of interest. Results: A total of 554 publications containing either of the query sets were identified. Following further assessment, 72 publications were included. The original research articles were scarce and the majority of them were in vitro studies. Conclusion: Sec61, Sec62, and Sec22B form a regulatory axis in bidirectional tumor-peptide trafficking across ER-associated compartments that governs antigen cross-presentation. By shaping antigen availability and immune recognition, these translocons may critically influence tumor behavior and represent promising targets for improving immunotherapeutic strategies in breast cancer.