Differential expression of cytokine transcripts in human epithelial ovarian carcinoma by solid tumour specimens peritoneal exudate cells containing tumour tumour-infiltrating lymphocyte (TIL)-derived T cell lines and established tumour cell lines

摘要

T cell lines derived in low concentrations of recombinant IL-2 (rIL-2) from TIL of patients with epithelial ovarian carcinoma (EOC) often exhibit specific cytotoxicity against autologous tumour cells. However, the ability of T cells at the tumour site to respond to ovarian carcinoma cells may be affected by the production of cytokines by the various cell types present. Using reverse transcriptase-polymerase chain reaction (RT-PCR) we investigated cytokine transcripts in: (i) established EOC tumour cell lines; (ii) solid tumour specimens or peritoneal exudate cells (PEC) from ascites or peritoneal washings of patients with EOC; and (iii) CD4⁺ TCRαβ⁺ and CD8⁺ TCRαβ⁺ TIL-derived T cell lines developed in rIL-2. We have found that (i) established EOC tumour cell lines expressed transcripts for transforming growth factor-beta 2 (TGF-β2) (7/7), but not IL-10 (0/7) or interferon-gamma (IFN-γ) (0/7) and rarely IL-2 (1/7); (ii) PEC expressed transcripts for IL-2 (12/13), IL-10 (9/13), and TGF-β2 (12/13), and less often, IFN-γ (3/13), whereas solid tumour specimens from eight patients with EOC expressed transcripts for IL-2 (4/8), TGF-β2 (4/8), and IL-10 (5/8), but not for IFN-γ (0/8); (iii) CD4⁺ TCRαβ⁺ T cell lines expressed transcripts for IFN-γ (4/4), IL-2 (4/4) and IL-10 (3/4), whereas CD8⁺ TCRαβ⁺ T cell lines expressed transcripts for IFN-γ (5/5), IL-2 (1/5) and IL-10 (2/5). None of these T cell lines expressed TGF-β2 transcripts. The frequency of IL-2 and TGF-β2 transcripts in solid tumours was significantly lower than in the PEC (P = 0.0475). CD4⁺ or CD8⁺ T cell lines expressing IFN-γ, IL-2 and IL-10 transcripts were derived in culture with rIL-2 from the TIL of specimens that did not necessarily express these cytokines in the absence of rIL-2. The frequency of cytokine transcripts in T cell lines compared with these same transcripts in the PEC was significantly higher for IFN-γ (P = 0.0005) and lower for TGF-β2 (P = 0.0001). An association was observed between the expression of cytokine transcripts in vivo or by TIL-derived cell lines and functions exhibited by either production of cytokines or in vitro cytotoxicity.