title: Loss of tapasin correlates with diminished CD8(+) T-cell immunity and prognosis in colorectal cancer.
abstract: BACKGROUND
  Tapasin is a crucial component of the major histocompatibility (MHC) class I antigen presentation pathway. Defects in this pathway can lead to tumor immune evasion. The aim of this study was to test whether tapasin expression correlates with CD8(+) cytotoxic T lymphocyte (CTL) infiltration of colorectal cancer (CRC) and overall survival.
  
  
  METHODS
  A next-generation tissue microarray (ngTMA) of 198 CRC patients with full clinicopathological information was included in this study. TMA slides were immunostained for tapasin, MHC I and CD8. Marker expression was analyzed with immune-cell infiltration, patient survival and TNM-staging.
  
  
  RESULTS
  A reduction of tapasin expression strongly correlated with venous invasion (AUC 0.682, OR 2.7, p = 0.002; 95% CI 1.7-5.0), lymphatic invasion (AUC 0.620, OR 2.0, p = 0.005; 95 % CI 1.3-3.3), distant metastasis (AUC 0.727, OR 2.9, p = 0.004; 95% CI 1.4-5.9) and an infiltrative tumor border configuration (AUC 0.621, OR 2.2, p = 0.017; 95% CI 1.2-4.4). Further, tapasin expression was associated with CD8(+) CTL infiltration (AUC 0.729, OR 5.4, p < 0.001; 95% CI 2.6-11), and favorable overall survival (p = 0.004, HR 0.6, 95% CI 0.42-0.85).
  
  
  CONCLUSIONS
  Consistent with published functional data showing that tapasin promotes antigen presentation, as well as tumor immune recognition and destruction by CD8(+) CTLs, a reduction in tapasin expression is associated with tumor progression in CRC.
authors: Translational Research Unit (TRU), Institute of Pathology, University of Bern, Murtenstrasse 31, 3010, Bern, Switzerland. Lena.sokol@pathology.unibe.ch.
authors: Lena
authors: L
authors: Sokol
authors: Translational Research Unit (TRU), Institute of Pathology, University of Bern, Murtenstrasse 31, 3010, Bern, Switzerland. viktor.koelzer@pathology.unibe.ch.|Clinical Pathology Division, Institute of Pathology, University of Bern, Murtenstrasse 31, 3010, Bern, Switzerland. viktor.koelzer@pathology.unibe.ch.
authors: Viktor H
authors: VH
authors: Koelzer
authors: Translational Research Unit (TRU), Institute of Pathology, University of Bern, Murtenstrasse 31, 3010, Bern, Switzerland. tilman.rau@pathology.unibe.ch.|Clinical Pathology Division, Institute of Pathology, University of Bern, Murtenstrasse 31, 3010, Bern, Switzerland. tilman.rau@pathology.unibe.ch.
authors: Tilman T
authors: TT
authors: Rau
authors: Translational Research Unit (TRU), Institute of Pathology, University of Bern, Murtenstrasse 31, 3010, Bern, Switzerland. eva.diamantis@pathology.unibe.ch.|Clinical Pathology Division, Institute of Pathology, University of Bern, Murtenstrasse 31, 3010, Bern, Switzerland. eva.diamantis@pathology.unibe.ch.
authors: Eva
authors: E
authors: Karamitopoulou
authors: Translational Research Unit (TRU), Institute of Pathology, University of Bern, Murtenstrasse 31, 3010, Bern, Switzerland. inti.zlobec@pathology.unibe.ch.
authors: Inti
authors: I
authors: Zlobec
authors: Translational Research Unit (TRU), Institute of Pathology, University of Bern, Murtenstrasse 31, 3010, Bern, Switzerland. alessandro.lugli@pathology.unibe.ch.|Clinical Pathology Division, Institute of Pathology, University of Bern, Murtenstrasse 31, 3010, Bern, Switzerland. alessandro.lugli@pathology.unibe.ch.
authors: Alessandro
authors: A
authors: Lugli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017951:Antigen Presentation; D019540:Area Under Curve; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D016017:Odds Ratio; D011379:Prognosis; D016016:Proportional Hazards Models; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology; D046888:Tissue Array Analysis
chemical_list: D015395:Histocompatibility Antigens Class I; D026901:Membrane Transport Proteins; C107762:tapasin