EXPRESSION OF MESSENGER-RNA FOR CYTOKINES IN TUMOR-INFILTRATING MONONUCLEAR-CELLS IN OVARIAN ADENOCARCINOMA AND INVASIVE BREAST-CANCER

Cytokine gene expression in tumor-infiltrating lymphocytes (TIL) in frozen-tissue sections of 2 types of human solid tumor-ovarian adenocarcinoma and invasive breast cancer-was examined by in situ hybridization with S-35-labeled cDNA probes for human cytokines. The proportion of cells containing mRNA able to hybridize to the antisense cDNA probes for interleukin 2 (IL-2), tumor necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma) or receptors for IL-2 (either p55 or p70) was also determined in human normal peripheral lymphoid tissues and inflammatory tissues. Few cells were positive for IL2 and TNF-alpha mRNA in reactive human lymph nodes and tonsils. Inflammatory lesions, such as salpingitis or chronic active hepatitis, contained 10-20 times more cells positive for cytokine mRNA than reactive lymphoid tissue. In contrast, tumor-infiltrating lymphocytes (TIL) in the stroma of ovarian carcinomas or most ductal breast tumors only rarely expressed mRNA for TNF-alpha, IL2 or IFN-gamma. The intensity of mononuclear cell infiltration in these tumors correlated positively with the percentage of cells which expressed mRNA for IL-2, TNF-alpha and IL-2R. In those ductal breast carcinomas which contained intracellular or intraductal mucins, up to 30% of lymphoid cells in the tumor stroma were positive for IL-2, TNF-alpha, IFN-gamma and IL-2R. Thus, strong evidence for local activation of mononuclear cells in situ, exemplified by the expression of genes for cytokines, was obtained only in inflammatory lesions and in mucin-producing breast carcinomas. In most carcinomas studied, few TIL expressed genes for cytokines as measured by in situ hybridization. Thus, human solid tumors appear to differ in their ability to induce gene expression for cytokines in TIL.