EFFECTS OF INTERLEUKIN-12 ON IN-VITRO CULTURE WITH INTERLEUKIN-2 OF REGIONAL LYMPH-NODE LYMPHOCYTES FROM LUNG-CANCER PATIENTS

In the present study, we carried out a functional analysis of regional lymph node lymphocytes (RLNL) from patients with lung cancer after in vitro activation by interleukin-2 (IL-2) and interleukin-12 (IL-12). IL-12 (100 U/ml) enhanced both the proliferation and cytotoxic activit y of RLNL in a culture with low doses of IL-2 (5-10 JRU/ml). After com paring an RLNL culture with a low dose of IL-2 alone, a higher proport ion of CD8(+) cells and CD56(+) cells and a lower proportion of CD4(+) cells were found in the culture with both IL-12 and a low dose of IL- 2. Such a combination of the cytokines effectively activated RLNL in t erms of the expression of IL-2 receptors. In the culture condition of IL-12 and a low dose of IL-2, a synergistic effect was observed in the production of such cytokines as interferon gamma, tumor necrosis fact or alpha (TNF alpha), and TNF beta, as well as in tumor cytotoxicity. However, the addition of IL-12 inhibited the cytotoxicity of RLNL in t he culture with a high dose of IL-2 (100 JRU/ml). This inhibition is c onsidered to be partially due to the endogenous production of TNF alph a by lymphocytes, because the neutralization of TNF alpha bioactivity partially restored the cytotoxic activities of RLNL. Furthermore, in t he presence of hydrocortisone, IL-12 synergistically enhanced the cyto toxic activity of RLNL cultured with a high dose of IL-2. These result s provide useful information about the improvement of adoptive immunot herapy against cancer using RLNL.