title: Control of T-cell-mediated immune response by HLA class I in human pancreatic carcinoma.
abstract: OBJECTIVE
  Cell surface HLA class I molecules present peptides derived from human cellular proteins to T cells. In the present study, we investigated the expression of HLA class I in human pancreatic carcinoma.
  
  
  METHODS
  The expression of HLA class I antigen and the extent of tumor infiltration by T cells were investigated in 46 primary tumors and in 14 metastases of pancreatic cancer by standard immunohistochemistry.
  
  
  RESULTS
  The locus-specific expression of HLA I was reduced in 61% of primary tumors and in 93% of metastases. The total loss of this molecule complex was detected in 6% of primary tumors and in 43% of metastases. Pancreatic carcinoma and peritumoral tissue showed a significantly higher infiltration by CD3+, CD4+, and CD8+ T-cells compared with the tumor-distant pancreatic tissue. The negative expression of HLA class I was uniformly accompanied by a low density of tumor-infiltrating cytotoxic T-cells whereas the HLA class I-positive tumors were characterized by a substantial lymphocyte accumulation. However, the infiltration by cytotoxic T-cells was not correlated with the density of tumor cells. Patients with a high accumulation of cytotoxic cells showed a longer median survival.
  
  
  CONCLUSIONS
  Pancreatic carcinoma frequently induces a cellular immune response that results in intratumoral and peritumoral T-cell infiltration. The expression of HLA class I is frequently lost in pancreatic carcinoma, which represents an effective mechanism to escape the tumor infiltration by cytotoxic T-cells. However, the infiltration by cytotoxic cells represents a favorable prognostic sign in pancreatic cancer patients.
authors.affiliation: Unit for Documentation and Statistics, Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
authors.forename: Eduard
authors.initials: E
authors.lastname: Ryschich
authors.forename: Tanja
authors.initials: T
authors.lastname: Nötzel
authors.forename: Ulf
authors.initials: U
authors.lastname: Hinz
authors.forename: Frank
authors.initials: F
authors.lastname: Autschbach
authors.forename: James
authors.initials: J
authors.lastname: Ferguson
authors.forename: Ioan
authors.initials: I
authors.lastname: Simon
authors.forename: Jürgen
authors.initials: J
authors.lastname: Weitz
authors.forename: Boris
authors.initials: B
authors.lastname: Fröhlich
authors.forename: Ernst
authors.initials: E
authors.lastname: Klar
authors.forename: Markus W
authors.initials: MW
authors.lastname: Büchler
authors.forename: Jan
authors.initials: J
authors.lastname: Schmidt
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology; D017252:CD3 Complex / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D002454:Cell Differentiation; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D010190:Pancreatic Neoplasms / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000276:immunology; D017154:Stromal Cells / Q000276:immunology / Q000473:pathology; D015996:Survival Rate; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic
chemical_list: D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I