Crosstalk between Tumor T Lymphocytes and Reactive T Lymphocytes in Cutaneous T Cell Lymphomas

Publisher Website
Google Scholar
Abstract
Abstract: We have established several tumor T cell lines, both from the skin and from the blood of a patient with an MHC class II−/class I+, CD4+ cutaneous T cell lymphoma (CTCL). These cell lines, like the initial tumor cells, had a CD3+CD4+CD8− phenotype. We also isolated two cytotoxic T lymphocyte clones from the tumor site of this CTCL patient. These clones displayed a CD4+CD8dim+ (TC5) and CD4+CD8− (TC7) phenotype and mediated a specific MHC class I‐restricted cytotoxic activity toward noncultured tumor cells and autologous tumor cell lines. Despite surface expression of Fas on tumor cells and Fas‐L induction on TC5 and TC7 cell membrane after coculture with autologous tumor cells, the CD4+ CTL clones did not use this cytotoxic mechanism to lyse their specific target. TC7 used a granzyme/perforin‐dependent pathway, whereas TC5 used a TRAIL‐dependent mechanism. Quantitative analysis of cytokine mRNA expression indicated that while the tumor cells displayed a Th2‐type profile, the CTL clones expressed Th1‐type cytokines. Pre‐incubation of TIL clones with autologous tumor cells in a short‐term culture induced their activation and subsequent amplification of the Th1‐type response, which indicates a direct contribution of the malignant cells in the Th1/Th2 imbalance. However, we found that tumor cells produced high amounts of TGF‐β, which could explain the inhibition of a specific antitumor immune response. Another mechanism to avoid the host immune response was the expression of CD158a, CD158b, p70, and CD94/NKG2A inhibitory receptors by tumor‐specific lymphocytes. Finally, we present recent data on new antigen structures expressed both by long‐term CTCL lines and uncultured tumor cells.