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Control of T-Cell–Mediated Immune Response by HLA Class I in Human Pancreatic Carcinoma

¹ Unit for Documentation and Statistics, Department of Surgery, and Departments of ² Surgery and ³ Pathology, University of Heidelberg, Heidelberg, Germany and ⁴ Department of Veterinary Surgery, University of Leipzig, Germany

Requests for reprints: Jan Schmidt, Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany. Phone: 49-6221-566204; Fax: 49-6221-565781; E-mail: Jan_Schmidt{at}med.uni-heidelberg.de.

Purpose: 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.

Experimental Design: 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.

Key Words: HLA class I • lymphocyte infiltration • pancreatic carcinoma

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