Control of T-cell-mediated immune response by HLA class I in human pancreatic carcinoma.
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.
Ryschich
Eduard
E
Unit for Documentation and Statistics, Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
Nötzel
Tanja
T
Hinz
Ulf
U
Autschbach
Frank
F
Ferguson
James
J
Simon
Ioan
I
Weitz
Jürgen
J
Fröhlich
Boris
B
Klar
Ernst
E
Büchler
Markus W
MW
Schmidt
Jan
J
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
D017252:CD3 Complex; D015704:CD4 Antigens; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I