INTERLEUKIN-1-BETA SYNERGISES WITH INTERLEUKIN-2 IN THE OUTGROWTH OF AUTOLOGOUS TUMOR-REACTIVE CD8+ EFFECTORS

Using peritoneal fluid or pleural effusion obtained from 20 patients with lung, ovarian or metastatic breast cancer, we separated tumour cells from malignant effusion-associated mononuclear cells (MEMNCs) using discontinuous Ficoll-Hypaque density gradients. CD3(+) T lymphocytes represented the main population of MEMNCs. The mean +/- s.d. CD4/CD8 ratio of MEMNC suspensions was 1.18 +/- 0.40 MEMNCs proliferated and expanded in vitro with human interleukin 2 (IL-2) either as CD3(+) CD8(+) cells or as CD3(+)CD4(+) cells or as mixed populations of CD8(+) and CD4(+) cells. Preferential cytolytic activity against autologous tumour cells was demonstrated in IL-2-activated MEMNC cultures with excess CD3(+)CD8(+) cells. In contrast, effecters derived from IL-2-activated cultures with excess CD3(+) CD4(+) cells lysed both autologous and allogeneic tumour target cells. The addition on day 0 of interleukin 1 beta (IL-1 beta) to MEMNCs cultured in the presence of IL-2 was effective in promoting the growth of CD3(+)CD8(+) cells and augmenting the cytotoxicity against autologous tumour. Simultaneously, the production of gamma-interferon (IFN-gamma) was increased in these cultures. This is the first report suggesting that IL-1 beta synergises with IL-2 to induce autologous tumour-specific CD8(+) cytotoxic T lymphocytes (CTLs) within the MEMNC population. Selective enrichment in T-cell subsets by IL-1 beta may be useful in cellular adoptive immunotherapy using cells isolated from malignant effusions.