TUMOR-HOST INTERACTION - ANALYSIS OF CYTOKINES, GROWTH-FACTORS, AND TUMOR-INFILTRATING LYMPHOCYTES IN OVARIAN CARCINOMAS

The host-tumor interaction may play an important role in determining t umor progress. Recent studies have shown that this interaction can be influenced by the release of soluble factors by tumor cells and tumor- infiltrating lymphocytes (TIL). The aim of our study is to characteriz e the nature of cytokines and growth factors and their relationship to the cellular infiltrates in 16 patients with ovarian cancer using rev erse transcriptase-polymerase chain reaction (RT-PCR) and immunohistoc hemistry. Total RNA from 20 malignant and 10 benign specimens were use d to assay for expression of 12 cytokines. Additionally, monoclonal an tibodies (MAbs) were used to detect T cells, CD4(+) helper and CD8(+) cytotoxic/suppressor T-cell subtypes, B cells, and macrophages. Our re sults showed the expression of transforming growth factor-beta(1) (TGF -beta(1)), interleukin-10 (IL-10), and granulocyte-macrophage colony-s timulating factor (GM-CSF) in 19, 17, and 10 malignant specimens, P < .001, .001, and .05, respectively. Other cytokines such as interferon- gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), TNF-beta/L T, IL-2, and IL-6 were expressed in a few cases, and IL-1 alpha and IL -4 expression were not detected. The benign samples did not express IL -10, but GM-CSF, TGF-beta(1), and IL-8 were expressed in one, one, and four specimens, respectively. Interestingly, in four cases in which s amples from the primary and relapse tumors were available for analysis , the tumors in relapse showed a significant increase for TGF-beta(1) (P < .05) and a decreased trend in IL-10 mRNA levels. The source of th ese factors was tumor cells as detected immunohistochemically. This co mbined alteration of TGF-beta(1) and IL-10 was associated with a signi ficant reduction in number of TIL in general, and CD8(+) and macrophag es in particular (P = .036 and .049, respectively). Our findings sugge st the important role of certain soluble factors in the complex proces s of tumor progression. Furthermore, understanding the tumor-host rela tionship and the factors influencing the interaction may be helpful in developing effective and innovative treatment methods. Copyright (C) 1997 by W.B. Saunders Company.