NONSMALL CELL LUNG CANCER-DERIVED SOLUBLE MEDIATORS AND PROSTAGLANDINE(2) ENHANCE PERIPHERAL-BLOOD LYMPHOCYTE IL-10 TRANSCRIPTION AND PROTEIN-PRODUCTION

Studies suggest that IL-10 may contribute to tumor-associated immunosu ppression, In the current study we evaluated the capacity of human non -small cell lung cancer (NSCLC) cell lines to induce PBL IL-10 product ion, We observed a 10- to 100-fold increase in human PBL IL-10 product ion following exposure to NSCLC cell supernatants. The tumor-induced i ncrease in PBL IL-10 production was partially blocked by pretreatment of the tumors with the PC inhibitor indomethacin, NSCLC lines were fou nd to constitutively produce PCE(2). Exogenous PGE(2) also induced PBL IL-10 production in a dose- and time-dependent manner, Both PCE, and NSCLC supernatant-induced PBL IL-10 production were due to an increase in the IL-10 mRNA transcriptional rate, To evaluate the significance of tumor-induced lymphocyte IL-10 production, the capacity of PBL to p roduce IFN-gamma during culture in tumor supernatants was assessed in the presence of specific anti-IL-10 mAb, We found enhanced PBL IFN-gam ma production following anti-IL-10 treatment, These in vitro studies i mply that NSCLC-induced PBL IL-10 production may serve to shift the Th 1/Th2 cytokine axis at the tumor site and thus inhibit cell-mediated a nti-tumor immune responses, These findings identify a mechanism by whi ch lung cancer cells may escape host immune surveillance, We conclude that NSCLC-derived soluble mediators, including PGs, may play an immun oregulatory role through induction of lymphocyte IL-10 production,