Relationships betxween Fas expression, activation molecule CD25, and functional activity of tumor-associated lymphomonocytes from neoplastic effusions.
Fas ligand (FasL), a cell surface molecule belonging to the tumor necrosis factor family, binds to its receptor Fas, thus inducing apoptosis of Fas bearing cells. In the present study we assessed the expression of Fas, activation molecule interleukin (IL)-2 receptor alpha chain (CD25) and an index of functional activity such as thymidine uptake under mitogen stimulation of tumor associated lymphomonocytes (TALM) from 7 neoplastic effusions of advanced cancer patients. The same parameters were studied in peripheral blood mononuclear cells (PBMC) of 7 patients with cancer of different sites and in 7 normal subjects. The proliferative response to phytohemagglutinin (PHA), measured as [3H]-thymidine uptake, of TALM was significantly lower than that of PBMC of cancer patients. The expression of CD25 on unstimulated fresh TALM was slightly higher than that of PBMC from normal subjects: after 24 h of PHA stimulation the CD25 was expressed both on TALM and PBMC from normal subjects. The expression of Fas was assessed on unstimulated TALM, PBMC from cancer patients and normal subjects immediately after (by 2 h, t0) the cell separation, and at different times (24 h and 48 h) thereafter, and on PHA-stimulated TALM, PBMC from cancer patients and normal subjects after 24 h and 48 h of culture (in RPMI 1640). At all times (t0, 24 h and 48 h) the Fas expression by unstimulated TALM was significantly higher than that of PBMC from normal subjects: the Fas expression by PBMC from cancer patients was roughly in the same range as PBMC from normal subjects. At 24 h the Fas expression by PHA-stimulated TALM was significantly higher than that of PBMC from normal subjects, whereas at 48 h the difference was not significant. The TALM studied by us showed to be functionally defective and expressing relatively high levels of Fas showing the characteristics to be considered as a target for FasL expressing tumor cells, which in this way may escape immune control.
Mantovani
G
G
Department of Medical Oncology, University of Cagliari, 09124 Cagliari, Italy.
Macciò
A
A
Massa
E
E
Lai
P
P
Manca
G
G
Mudu
C
C
Versace
R
R
Pusceddu
G
G
D000328:Adult; D000368:Aged; D001202:Ascitic Fluid / Q000166:cytology*; D004261:DNA Replication; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000502:physiology; D008213:Lymphocyte Activation / Q000187:drug effects*; D016246:Lymphocytes, Tumor-Infiltrating / Q000737:chemistry / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D010835:Phytohemagglutinins / Q000494:pharmacology; D016066:Pleural Effusion, Malignant / Q000166:cytology*; D015375:Receptors, Interleukin-2 / Q000502:physiology*; D019014:fas Receptor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D009363:Neoplasm Proteins; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; D019014:fas Receptor