Abstract
Tumor cells from five freshly isolated ovarian tumors and four established human ovarian carcinoma cell lines were analyzed for the production of the immunoinhibitory cytokine transforming growth factor-beta (TGF-beta) before and after exposure to gamma irradiation and/or the cytokines TNF-alpha plus IFN-gamma. All fresh tumors secreted high levels of TGF-beta when compared to the levels produced by the established ovarian carcinoma cell lines. TGF-beta produced by fresh tumors was significantly reduced after high doses of gamma irradiation (10,000 cGy). In contrast with the established cell lines, irradiation significantly increased TGF-beta secretion. Exposure of fresh tumor cells to cytokines followed by irradiation caused significant reduction of TGF-beta released when compared to the amount released after exposure to cytokines only. However, in the established cell lines, cytokines followed by irradiation again significantly increased TGF-beta production. These data indicate that high doses of irradiation in fresh ovarian tumors, unlike established ovarian carcinoma cell lines, can significantly reduce the local production of this potent immunoinhibitory cytokine. This effect could work to further amplify weak immunological responses within the tumor. In addition, these findings indicate major differences between fresh tumor samples and established cell lines and warn against the sole use of continuous cell lines as models for tumors growing in vivo.
Highlights
Ovarian carcinoma remains the fourth most frequent cause of cancer death in women in the United States and Europe.Because of the insidious onset and progression of this disease, about 75% of patients initially present with tumor disseminated throughout the peritoneal cavity
Because ovarian cancer remains confined to the peritoneal cavity even in advanced stages of the disease it has been suggested that the growth of this malignancy could be related to a local phenomenon of immunosuppression [4, 5]
We have recently developed human ovarian carcinoma tumor vaccines secreting different cytokines to be used as vaccines for women with advanced ovarian cancer [23, 24]
Summary
Ovarian carcinoma remains the fourth most frequent cause of cancer death in women in the United States and Europe.Because of the insidious onset and progression of this disease, about 75% of patients initially present with tumor disseminated throughout the peritoneal cavity. Because ovarian cancer remains confined to the peritoneal cavity even in advanced stages of the disease it has been suggested that the growth of this malignancy could be related to a local phenomenon of immunosuppression [4, 5]. Several studies have documented the local deficiency of antitumor immune effector mechanisms in the peritoneal cavity of patients with advanced stages of ovarian cancer [4, 5]. While some of these immunosuppressive factors have been identified as cytokine receptors shed into the ascitic fluid [3, 6], others have been identified as inhibitory cytokines [7, 8]
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