title: HLA class I is most tightly linked to levels of tapasin compared with other antigen-processing proteins in glioblastoma.
abstract: 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.
authors: Immunology Section, Department of Experimental Medical Science, Lund University, SE-221 84 Lund, Sweden.
authors: Camilla
authors: C
authors: Thuring
authors: Immunology Section, Department of Experimental Medical Science, Lund University, SE-221 84 Lund, Sweden.
authors: Elna
authors: E
authors: Follin
authors: Immunology Section, Department of Experimental Medical Science, Lund University, SE-221 84 Lund, Sweden.
authors: Linda
authors: L
authors: Geironson
authors: Science for Life Laboratory, Bioinformatics Infrastructure for Life Sciences, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine, Uppsala University, SE-751 05 Uppsala, Sweden.
authors: Eva
authors: E
authors: Freyhult
authors: Immunology Section, Department of Experimental Medical Science, Lund University, SE-221 84 Lund, Sweden.
authors: Victoria
authors: V
authors: Junghans
authors: Department of Experimental Immunology, Institute of International Health, Immunology and Microbiology, DK-2200 Copenhagen, Denmark.
authors: Mikkel
authors: M
authors: Harndahl
authors: Department of Experimental Immunology, Institute of International Health, Immunology and Microbiology, DK-2200 Copenhagen, Denmark.
authors: Søren
authors: S
authors: Buus
authors: Immunology Section, Department of Experimental Medical Science, Lund University, SE-221 84 Lund, Sweden.
authors: Kajsa M
authors: KM
authors: Paulsson
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000626:Aminopeptidases / Q000378:metabolism; D001932:Brain Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000378:metabolism; D005909:Glioblastoma / Q000276:immunology / Q000378:metabolism* / Q000401:mortality / Q000628:therapy; D006680:HLA Antigens / Q000276:immunology / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy; D026901:Membrane Transport Proteins / Q000378:metabolism*; D015778:Minor Histocompatibility Antigens; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D001613:beta 2-Microglobulin / Q000378:metabolism
chemical_list: D018528:ATP-Binding Cassette Transporters; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D026901:Membrane Transport Proteins; D015778:Minor Histocompatibility Antigens; D001613:beta 2-Microglobulin; C107762:tapasin; C477327:transporter associated with antigen processing (TAP); C071313:LMP-2 protein; D000626:Aminopeptidases; C464841:ERAP1 protein, human; C503944:ERAP2 protein, human; D003546:Cysteine Endopeptidases; C077436:LMP7 protein; D046988:Proteasome Endopeptidase Complex