Immunosuppressive mechanisms in the microenvironment of malignant pleural effusions.
Malignant effusions in serous cavities constitute a unique milieu for direct contact of tumor cells with host lymphoid cells in a fluid phase. The aim of this study was to depict agents responsible for suppression of lymphoid cells with putative anti-tumor potential. Pleural effusions drawn from 44 (18 non-malignant and 26 malignant) patients were tested for selected cytokines--interleukin-10 (IL-10), transforming growth factor beta (TGF-beta1) and soluble Fas ligand (sFasL) and nuclear membrane proteins (NMPs) content by ELISA. TCR-zeta expression of T cells and TUNEL reaction for apoptosis were evaluated by three color flow cytometry. 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 sFasL content. Moreover, NMPs corresponding to decoy cell fragments, were also heightened in MPE. Concentrations of NMPs correlated with the percent of apoptotic (TUNEL+) T CD3+ lymphocytes and inversely correlated with the percent of T cells. The low expression of TCR-zeta chain on T cells corresponded to high concentration of sFasL in MPE. In conclusion, the above data suggest that out of three suppression agents tested, only sFasL appears to show correlation with the downregulation of T cells in MPE.
Sikora
Jan J
JJ
University of Medical Sciences, 49 Przybyszewski Str., Poznań, Poland. jan-sikora@wp.pl
Dworacki
Grzegorz T
GT
Kaczmarek
Mariusz T
MT
Jenek
Renata E
RE
Zeromski
Jan O
JO
D017209:Apoptosis; D016207:Cytokines / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007165:Immunosuppression Therapy; D020287:In Situ Nick-End Labeling; D016753:Interleukin-10 / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D016066:Pleural Effusion, Malignant / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000097:blood; D053773:Transforming Growth Factor beta1
D016207:Cytokines; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10