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.
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+ TCRalphabeta+ and CD8+ TCRalphabeta+ 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-beta2) (7/7), but not IL-10 (0/7) or interferon-gamma (IFN-gamma) (0/7) and rarely IL-2 (1/7); (ii) PEC expressed transcripts for IL-2 (12/13), IL-10 (9/13), and TGF-beta2 (12/13), and less often, IFN-gamma (3/13), whereas solid tumour specimens from eight patients with EOC expressed transcripts for IL-2 (4/8), TGF-beta2 (4/8), and IL-10 (5/8), but not for IFN-gamma (0/8); (iii) CD4+ TCRalphabeta+ T cell lines expressed transcripts for IFN-gamma (4/4), IL-2 (4/4) and IL-10 (3/4), whereas CD8+ TCRalphabeta+ T cell lines expressed transcripts for IFN-gamma (5/5), IL-2 (1/5) and IL-10 (2/5). None of these T cell lines expressed TGF-beta2 transcripts. The frequency of IL-2 and TGF-beta2 transcripts in solid tumours was significantly lower than in the PEC (P = 0.0475). CD4+ or CD8+ T cell lines expressing IFN-gamma, 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-gamma (P = 0.0005) and lower for TGF-beta2 (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.
Nash
M A
MA
Department of Gynecological Oncology, The University of Texas, M. D. Anderson Cancer Center, Houston 77030, USA.
Lenzi
R
R
Edwards
C L
CL
Kavanagh
J J
JJ
Kudelka
A P
AP
Verschraegen
C F
CF
Platsoucas
C D
CD
Freedman
R S
RS
D000230:Adenocarcinoma / Q000378:metabolism; D001202:Ascitic Fluid / Q000473:pathology*; D002277:Carcinoma / Q000378:metabolism*; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D013499:Surface Properties; D016176:T-Lymphocyte Subsets / Q000378:metabolism*; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured
D016207:Cytokines; D016212:Transforming Growth Factor beta