Immunosuppressive mechanisms in the microenvironment of malignant pleural effusions

Jan Zeromski MD, PhD, Renata Jenek PhD, Mariusz Kaczmarek BS, Grzegorz Dworacki, MD and Jan Sikora PhD.

Dept. Clinical Immunology, Karol Marcinkowski University of Medical Sciences Poznan, Poland.

Malignant effusions in serous cavities constitute a unique milieu for the direct contact of tumor cells with host lymphoid cells in a fluid phase. AIM of this study was to depict agents responsible for suppression of lymphoid cells with putative anti-tumor potential. METHODS -pleural effusions drawn from 20 cancer patients and suitable control ones were tested for selected cytokines - IL-10, TGF-beta and besides soluble Fas Ligand (sFas L) and nuclear membrane proteins (NMPs) content by means ELISA. TCR zeta expression of T cells and TUNEL reaction for apoptosis were evaluated by three color flow cytometry. RESULTS - both cytokine concentrations were found to be significantly elevated in malignant pleural effusions (MPE) as compared to non-malignant ones. It was also true for sFas L content. Moreover, NMPs corresponding to decoy cell fragments, were also heightened in MPE. Concentrations of NMPs were correlated with the percent of apoptotic (TUNEL+) T CD3+ lymphocytes and inversely correlated to the percent of T cells. The low expression of TCR zeta chain on T cells corresponded to the high concentration of sFas L in (MPE). CONCLUSIONS: The above data suggest that out of three suppression agents tested, only sFasL appears to be directly linked to downregulation of T cells in MPE.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Diagnostic Markers.