Abstract:
The variable clinical response seen with most cancer immunotherapy suggests that individual patients have very different immunological mechanisms involved in the pathophysiology of their specific malignancy. These can include important differences in tumor antigens on the malignant cells, as well as the specific immune response to the tumor. One of the key functional parameters of an immune response is the local production of cytokines. As a method to survey the immune status of TIL cells, we have investigated the constitutive expression of cytokine mRNA in biopsies from ovarian cell carcinomas using a PCR-assisted mRNA amplification assay. Using a set of cytokine-specific primers for 10 different cytokines, we have found a selective expression of IL-10, GM-CSF and IFN-gamma mRNA in the ovarian tumor tissue, as compared with normal ovaries and ovarian tumor cell lines. Such a cytokine profile is characteristic of the T(H)1 CD4+ and cytotoxic CD8+ cells. No IL-2 gene expression was detected in the tumor biopsies. However, TIL cells expressed IL-2 mRNA after stimulation via the CD3 molecule. Using the same cDNA-PCR method, experiments were also performed to correlate the cytokine mRNA pattern of each tumor biopsy with its TCR V beta gene repertoire. No restriction or clonality in this specific gene usage was observed.
Keywords: Antigens, CD3 CD4-CD8 Ratio DNA/GENETICS Gene Amplification *Gene Expression Genes, Immunoglobulin Granulocyte-Macrophage Colony-Stimulating Factor/*GENETICS Interferon Type II/GENETICS/*METABOLISM Interleukin-10/GENETICS/*METABOLISM Interleukin-2/METABOLISM Lymphocytes, Tumor-Infiltrating/METABOLISM Ovarian Neoplasms/GENETICS/*METABOLISM/PATHOLOGY Polymerase Chain Reaction Receptors, Antigen, T-Cell/GENETICS RNA, Messenger/METABOLISM Tumor Cells, Cultured ABSTRACT 930228
M9320866
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