Cancer Res Treat.  2019 Jan;51(1):80-89. 10.4143/crt.2017.500.

Expression of Immunoproteasome Subunit LMP7 in Breast Cancer and Its Association with Immune-Related Markers

• Lee M
• Song IH
• Heo SH
• Kim YA
• Park IA
• Bang WS
• Park HS
• Gong G
• Lee HJ

• KMID: 2437601
• DOI: http://doi.org/10.4143/crt.2017.500

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.

Keyword

Immunoproteasome; Breast neoplasms; LMP7; Tumor-infiltrating lymphocytes; Interferons; HLA antigens

MeSH Terms

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
HLA Antigens
HMGB1 Protein
Interferons
Peptides
Proteasome Endopeptidase Complex

Figure

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  Fig. 1. Immunohistochemical staining of LMP7 in breast cancer tissues. Representative images are shown (×200).

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  Fig. 2. Heat map plot for LMP7 expression with interferon-associated molecules, endoplasmic reticulum stress-associated molecules, damage-associated molecular patterns, and amount of tumor-infiltrating lymphocytes.

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  Fig. 3. Relationship between LMP7 expression and disease-free survival in the triple-negative breast cancer cohort. Kaplan-Meier survival curves are shown for disease-free survival in the group of positive lymph node (LN) metastases and in the group of negative LN metastases.

Reference

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