title: Tapasin and human leukocyte antigen class I dysregulation correlates with survival in glioblastoma multiforme.
abstract: Human leukocyte antigen class I (HLA-I) molecules present antigenic peptides to cytotoxic CD8(+) T cells. Downregulation of peptide:HLA-I complexes is common in tumors and results in tumor immune escape variants. Also molecules involved in the maturation of HLA-I have been demonstrated to be dysregulated in malignant neoplasms. We here set out to investigate the antigen presentation capabilities of a set of 12 glioblastoma multiforme (GBM) tumors based on the expression of HLA-I. Moreover, we analyzed the expression of tapasin, a protein dedicated and essential to HLA-I maturation, as well as the infiltration of CD8+ cells using immunohistochemistry on paraffin-embedded sections. Comparison of different GBMs showed a variation in expression of both HLA-I heavy chain (HC) and tapasin. Interestingly, the expression of tapasin and HLA-I HC correlated significantly (p=0.0002) suggesting tapasin to be a key factor for efficient HLA-I antigen presentation in GBMs. Although no statistically significant correlation between CD8(+) cells and survival was found, probably due to a very low number of infiltrating CD8(+) cells at the time of surgical resection, both tapasin and HLA-I HC levels significantly correlated with survival. We suggest that analysis of expression of tapasin and/or HLA-I may be of value as prognostic tool for GBM patients, especially when considering immunotherapy.
authors.forename: Camilla
authors.initials: C
authors.lastname: Thuring
authors.forename: Linda
authors.initials: L
authors.lastname: Geironson
authors.affiliation: Immunology, Lund University, BMC D14, 221 84 Lund, Sweden. Kajsa_M.Paulsson@med.lu.se.
authors.forename: Kajsa
authors.initials: K
authors.lastname: Paulsson
mesh_terms: D000368:Aged; D001932:Brain Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D005909:Glioblastoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D006680:HLA Antigens / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D015996:Survival Rate
chemical_list: D006680:HLA Antigens; D026901:Membrane Transport Proteins; C107762:tapasin