Effector T lymphocyte subsets in human pancreatic cancer: detection of CD8+ CD18+ cells and CD8+ CD103+ cells by multi-epitope imaging

Pancreatic cancer is characterized by an increasing incidence and an extremely poor prognosis. It is resistant to most of the conventional treatment modalities. Histomorphologically, it presents with a strong desmoplastic reaction around cancer cells, and lymphocytes are typically localized as aggregates in the fibrotic interstitial tissue. Using the method of multi-epitope imaging with fluorochrome-tagged specific MoAbs which allows the simultaneous localization and characterization of T cells in tissues, we studied phenotypes and distribution of tumour-infiltrating lymphocytes (TIL) in pancreatic cancer. CD3⁺ T cells comprised up to 90% of the tumour-infiltrating cells which were either CD4⁺ or CD8⁺, most of them being memory cells (CD45RO⁺). In decreasing order of frequency, T lymphocytes carried the markers for CD45RO, CD18, CD103 and TCR γδ. Very few natural killer cells (CD56⁺) were observed. Twenty percent of CD8⁺were labelled with CD103. These CD8⁺ CD103⁺T cells, analogous to the gut intraepithelial lymphocytes (IEL), were found in the fibrous interstitial tissue. Furthermore, an inverse correlation was found between the expression of CD18, the β₂-integrin, which mediates adhesion of activated lymphocytes, and CD45RO in the CD8⁺subset of TIL (P = 0.046). In conclusion, phenotyping of T lymphocytes in pancreatic cancer raises the possibility that pancreatic cancer cells develop several strategies to escape the T cell-induced cytolysis by (i) the aggregation of cytotoxic CD8⁺ CD103⁺ T cells in the fibrous tissue distant from the tumour cells, and (ii) the presence of CD18-bearing cells which lack the expression of the activation marker CD45RO.