Prognostic Association of Immunoproteasome Expression and its Correlation with Tumor-Infiltrating Lymphocytes in Breast Cancer

Abstract

The proteasome system is the central proteolytic system of eukaryotic cells and is crucial for maintaining protein homeostasis by degrading misfolded or unwanted proteins into smaller peptides. Immunoproteasomes, which are specialized proteasomal complexes, enhance antigen processing for MHC class I presentation, influencing T cell-mediated responses. IP is predominantly found in immune cells and can be induced in non-immune cells by IFN-γ and TNF-α. The Immunoproteasome complex has three active subunits in the catalytic core- β5i, β1i and β2i. The difference in constitutive proteasome and immunoproteasome catalytic activities is the enhanced chymotrypsin-like activity of the IP subunits, which in the tumor microenvironment helps shape the repertoire of neo-antigens. So, the immunoproteasome is involved in the modulation of chronic inflammatory environments, as well as in optimal antigen presentation of tumor epitopes to the tumor-infiltrating CD8+ T cells. However, their expression in the tumor and tumor-infiltrating lymphocytes (TILs) and its relationship with TILs remain poorly understood in breast cancer. Using immunohistochemistry, we found that LMP7(β5i) and PSMB10 (β2i) expression in tumor had a significant positive correlation, suggesting co-regulation. Moreover, high IP subunit expression in tumor negatively correlated with the TILs infiltration. We also saw a negative association of IP subunit expression with the prognosis of the patient. A previous study on TILs had reported that a higher TILs score corresponded to better survival of the patient. Our study matches with this result in the sense that higher IP expression would lead to less immune infiltration and poor prognosis, and less immune infiltration would also lead to a poor prognosis, thereby establishing a concordance with the study.