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HLA class I is most tightly linked to levels of tapasin compared with other antigen-processing proteins in glioblastoma
Lund Univ, Immunol Sect, Dept Expt Med Sci, SE-22184 Lund, Sweden..
Lund Univ, Immunol Sect, Dept Expt Med Sci, SE-22184 Lund, Sweden..
Lund Univ, Immunol Sect, Dept Expt Med Sci, SE-22184 Lund, Sweden..
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
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2015 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 113, no 6, 952-962 p.Article in journal (Refereed) Published
Abstract [en]

Background: Tumour cells can evade the immune system by dysregulation of human leukocyte antigens (HLA-I). Low quantity and/or altered quality of HLA-I cell surface expression is the result of either HLA-I alterations or dysregulations of proteins of the antigen-processing machinery (APM). Tapasin is an APM protein dedicated to the maturation of HLA-I and dysregulation of tapasin has been linked to higher malignancy in several different tumours. Methods: We studied the expression of APM components and HLA-I, as well as HLA-I tapasin-dependency profiles in glioblastoma tissues and corresponding cell lines. Results: Tapasin displayed the strongest correlation to HLA-I heavy chain but also clustered with beta(2)-microglobulin, transporter associated with antigen processing (TAP) and LMP. Moreover, tapasin also correlated to survival of glioblastoma patients. Some APM components, for example, TAP1/TAP2 and LMP2/LMP7, showed variable but coordinated expression, whereas ERAP1/ERAP2 displayed an imbalanced expression pattern. Furthermore, analysis of HLA-I profiles revealed variable tapasin dependence of HLA-I allomorphs in glioblastoma patients. Conclusions: Expression of APM proteins is highly variable between glioblastomas. Tapasin stands out as the APM component strongest correlated to HLA-I expression and we proved that HLA-I profiles in glioblastoma patients include tapasin-dependent allomorphs. The level of tapasin was also correlated with patient survival time. Our results support the need for individualisation of immunotherapy protocols.

Place, publisher, year, edition, pages
2015. Vol. 113, no 6, 952-962 p.
Keyword [en]
tapasin, HLA-I, glioblastoma multiforme, peptide, tapasin-dependency, immunotherapy
National Category
Cancer and Oncology
URN: urn:nbn:se:uu:diva-264630DOI: 10.1038/bjc.2015.297ISI: 000361499300012PubMedID: 26313662OAI: oai:DiVA.org:uu-264630DiVA: diva2:862742
Swedish Research CouncilThe Crafoord Foundation
Available from: 2015-10-23 Created: 2015-10-15 Last updated: 2015-10-23Bibliographically approved

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Freyhult, Eva
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