HLA class I is most tightly linked to levels of tapasin compared with other antigen-processing proteins in glioblastoma
| Autor: | Victoria Junghans, Eva Freyhult, Kajsa M Paulsson, Elna Follin, Camilla Thuring, Mikkel Harndahl, Linda Geironson, Søren Buus |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Proteasome Endopeptidase Complex
Cancer Research medicine.medical_treatment Cell Human leukocyte antigen Aminopeptidases Minor Histocompatibility Antigens glioblastoma multiforme Immune system tapasin Tapasin HLA Antigens Cell Line Tumor medicine Minor histocompatibility antigen Humans HLA-I Molecular Diagnostics biology Brain Neoplasms Membrane transport protein Antigen processing Histocompatibility Antigens Class I Membrane Transport Proteins Immunotherapy peptide Cysteine Endopeptidases medicine.anatomical_structure Oncology biology.protein Cancer research ATP-Binding Cassette Transporters tapasin-dependency immunotherapy Corrigendum Glioblastoma beta 2-Microglobulin |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | 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 β2-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. |
| Databáze: | OpenAIRE |
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