Expression of Immunoproteasome Subunit LMP7 in Breast Cancer and Its Association with Immune-Related Markers
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
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 cellmediated 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.
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 cellmediated 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.
참고문헌 (20)
- van Rooijen JM, "Immunotherapeutic options on the horizon in breast cancer treatment", Pharmacol Ther, 156, pp.90~101 (2015)
- Kast J., "Immunoproteasome deficiency in non-small cell lungcancer and its relevance to immunotherapy", J Thorac Dis, 8, pp.E1082~E1086 (2016)
- Shashova EE, "Proteasome functioning in breast cancer: connection with clinical-pathological factors", PLoS One, 9, pp.e109933~ (2014)
- Kaur G, "Emerging role of immunoproteasomes in pathophysiology", Immunol Cell Biol, 94, pp.812~820 (2016)
- Kim JY, "Activation of the PERK-eIF2alpha pathway is associated with tumor-infiltrating lymphocytes in HER2-positive breast cancer", Anticancer Res, 36, pp.2705~2711 (2016)
- Lee HJ, "Tertiary lymphoid structures : prognostic significance and relationship with tumour-infiltrating lymphocytes in triple-negative breast cancer", J Clin Pathol, 69, pp.422~430 (2016)
- Lee HJ, "Differential expression of major histocompatibility complex class I in subtypes of breast cancer is associated with estrogen receptor and interferon signaling", Oncotarget, 7, pp.30119~30132 (2016)
- Park IA, "Endoplasmic reticulum stress induces secretion of highmobility group proteins and is associated with tumor-infiltrating lymphocytes in triple-negative breast cancer", Oncotarget, 7, pp.59957~59964 (2016)
- Kim YA, "MxA expression is associated with tumor-infiltrating lymphocytes and is a prognostic factor in triple-negative breast cancer", Breast Cancer Res Treat, 156, pp.597~606 (2016)
- Lee HJ, "Low prognostic implication of fibroblast growth factor family activation in triple-negative breast cancer subsets", Ann Surg Oncol, 21, pp.1561~1568 (2014)
- Hammond ME, "American Society of Clinical Oncology", College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version), 2010, pp.134, e48~e72
- Wolff AC, "Recommendations for human epidermal growth factor receptor 2 testing in breast cancer : American Society of Clinical Oncology", College of American Pathologists clinical practice guideline update, 2014, pp.138, 241~256
- Torigoe T, "Establishment of a monoclonal anti-pan HLA class I antibody suitable for immunostaining of formalin-fixed tissue : unusually high frequency of down-regulation in breast cancer tissues", Pathol Int, 62, pp.303~308 (2012)
- Cancer Genome Atlas Network, "Comprehensive molecular portraits of human breast tumours", Nature, 490, pp.61~70 (2012)
- Cabrera CM, "Total loss of MHC class I in colorectal tumors can be explained by two molecular pathways : beta2-microglobulin inactivation in MSI-positive tumors and LMP7", TAP2 downregulation in MSI-negative tumors, 2003, pp.61, 211~219
- Miller Z, "Inhibitors of the immunoproteasome:current status and future directions", Curr Pharm Des, 19, pp.4140~4151 (2013)
- Rouette A, "Expression of immunoproteasome genes is regulated by cell-intrinsic and-extrinsic factors in human cancers", Sci Rep, 6, pp.34019~ (2016)
- 이희진, "Tumor-Associated Lymphocytes Predict Response to Neoadjuvant Chemotherapy in Breast Cancer Patients", Journal of Breast Cancer, 16(1), pp.32~39 (2013), 한국유방암학회[DOI]
- 이소정, "Expression of Myxovirus Resistance A (MxA) Is Associated with Tumor-Infiltrating Lymphocytes in Human Epidermal Growth Factor Receptor 2 (HER2)–Positive Breast Cancers", Cancer Research and Treatment, 49(2), pp.313~321 (2017), 대한암학회
- Ma W, "A MAGE-C2 antigenic peptide processed by the immunoproteasome is recognized by cytolytic T cells isolated from a melanoma patient after successful immunotherapy", Int J Cancer, 129, pp.2427~2434 (2011)