Open AccessDifferential 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
Author(s) -
M. Nash,
Renato Lenzi,
Cynthia Edwards,
John J. Kavanagh,
Andrzej P. Kudelka,
Claire F. Verschraegen,
Chris D. Platsoucas,
Ralph S. Freedman
Publication year - 1998
Publication title -
clinical & experimental immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 135
eISSN - 1365-2249
pISSN - 0009-9104
DOI - 10.1046/j.1365-2249.1998.00576.x
Subject(s) - biology , cd8 , ovarian carcinoma , cytokine , cytotoxic t cell , cell culture , cancer research , t cell receptor , t cell , microbiology and biotechnology , ovarian cancer , immunology , antigen , immune system , in vitro , cancer , biochemistry , genetics
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.