Expression of Immunoproteasome Subunit LMP7 in Breast Cancer and Its Association with Immune-Related Markers.
- Author:
Miseon LEE
1
;
In Hye SONG
;
Sun Hee HEO
;
Young Ae KIM
;
In Ah PARK
;
Won Seon BANG
;
Hye Seon PARK
;
Gyungyub GONG
;
Hee Jin LEE
Author Information
- Publication Type:Original Article
- Keywords: Immunoproteasome; Breast neoplasms; LMP7; Tumor-infiltrating lymphocytes; Interferons; HLA antigens
- MeSH: Antigen Presentation; Breast Neoplasms*; Breast*; Cohort Studies; Disease-Free Survival; Endoplasmic Reticulum; HLA Antigens; HMGB1 Protein; Humans; Immune System; Interferons; Lymph Nodes; Lymphocytes, Tumor-Infiltrating; Neoplasm Metastasis; Peptides; Proteasome Endopeptidase Complex; Triple Negative Breast Neoplasms
- From:Cancer Research and Treatment 2019;51(1):80-89
- CountryRepublic of Korea
- Language:English
- Abstract: PURPOSE: In the presence of interferon, proteasome subunits are replaced by their inducible counterparts to form an immunoproteasome (IP) plays a key role in generation of antigenic peptides presented by MHC class I molecules, leading to elicitation of a T cell‒mediated immune response. Although the roles of IP in other cancers, and inflammatory diseases have been extensively studied, its significance in breast cancer is unclear. MATERIALS AND METHODS: We investigated the expression of LMP7, an IP subunit, and its relationship with immune system components in two breast cancer cohorts. RESULTS: In 668 consecutive breast cancer cohort, 40% of tumors showed high level of LMP7 expression, and tumors with high expression of LMP7 had more tumor-infiltrating lymphocytes (TILs) in each subtype of breast cancer. In another cohort of 681 triple-negative breast cancer patients cohort, the expression of LMP7 in tumor cells was significantly correlated with the amount of TILs and the expression of interferon-associated molecules (MxA [p < 0.001] and PKR [p < 0.001]), endoplasmic reticulum stress-associated molecules (PERK [p=0.012], p-eIF2a [p=0.001], and XBP1 [p < 0.001]), and damage-associated molecular patterns (HMGN1 [p < 0.001] and HMGB1 [p < 0.001]). Patients with higher LMP7 expression had better disease-free survival outcomes than those with no or low expression in the positive lymph node metastasis group (p=0.041). CONCLUSION: Close association between the TIL levels and LMP7 expression in breast cancer indicates that better antigen presentation through greater LMP7 expression might be associated with more TILs.
