QUANTITATIVE-ANALYSIS OF TH1, TH2 AND TGF-BETA-1 CYTOKINE EXPRESSION IN TUMOR, TIL AND PBL OF NONSMALL CELL LUNG-CANCER PATIENTS

For understanding the local immune response in human non-small cell lu ng cancer (NSCLC), we investigated both Th1 and Th2-type as well as TG F-beta 1 cytokine mRNA expression in 10 fresh tumor biopsies, the corr esponding tumor and short term TIL cell lines as well as patient PBMC. A methodology based on a highly sensitive quantitative RT-FCR was use d. We found that IL-6 mRNA was highly expressed in all tumor biopsy sa mples analyzed (4 LLC, 3 ADC and 3 SCC). IL-10 mRNA was expressed in 7 of 10 biopsies whereas IL-4 mRNA expression was moderate. Analysis of type I cytokines revealed a low expression level of IL-2 mRNA, while IFN gamma and GM-CSF expression was high in the majority of the tumor lesions studied, Quantitatively, high amounts of Th2-type cytokine mRN A were detected at the tumor site with IL-6 as the predominant lymphok ine. A high mRNA expression level of the immunosuppressive cytokine TG F-beta 1 was observed in all NSCLC, To identify the cell types respons ible for the production of TGF-beta 1, IL-6, IL-10 and GM-CSF at the t umor site, tumor and TIL cell lines were derived from the correspondin g biopsies. All the 3 tumor cell lines analysed were found to express high amount of TGF-beta 1but not IL-10RNA, 2 expressing IL-6 and GM-CS F, Five short term TIL cell lines established in the presence of IL-2 expressed high level of IL-10, IL-4 and IFN gamma but not IL-2 mRNA, S trikingly, high expression of IL-10 mRNA was also observed in all 6 pa tient PBMC analyzed as compared to controls. Together, our results ind icate the existence of a local and peripheral Th-2type cytokine patter n in patients bearing NSCLC, (C) 1998 Wiley-Liss, Inc.