Soluble Fas ligand released by colon adenocarcinoma cells induces host lymphocyte apoptosis: an active mode of immune evasion in colon cancer.
Expression of membrane-bound Fas ligand (mFasL) on colon cancer cells serves as a potential mechanism to inhibit host immune function by inducing apoptosis of host lymphocytes. Membrane-bound FasL can be cleaved and released as a soluble mediator (sFasL), which may spread the apoptosis induction effect. Our study examined whether colon adenocarcinoma cells release sFasL, and induce apoptosis of host lymphocytes without direct cell-cell contact. In 12 consecutive patients with colon adenocarcinoma mFasL was identified in the tumours, sFasL was measured in the sera and apoptosis identified in tumour-infiltrating and peripheral blood lymphocytes. To analyse the function of sFasL, colon cancer cells were primarily cultured; sFasL was isolated from supernatants, measured, incubated with Fas-bearing Jurkat cells, and the resulting apoptosis was analysed. Serum levels of sFasL were significantly elevated in all colon cancer patients with mFasL expression in tumour tissues (n = 8). In these patients, the number of apoptotic lymphocytes was significantly increased within tumour and peripheral blood. Furthermore, sFasL was present in the corresponding supernatants and induced apoptosis of Jurkat cells in a dose-dependent manner. These findings suggest that mFasL-positive colon cancer cells release sFasL, and thus may induce apoptosis of host lymphocytes as a potential mechanism for immune evasion.
Song
E
E
Department of Medicine, University Hospital Essen, Hufelandstr. 55, 45122 Essen, Germany.
Chen
J
J
Ouyang
N
N
Su
F
F
Wang
M
M
Heemann
U
U
D000230:Adenocarcinoma / Q000276:immunology* / Q000503:physiopathology*; D000368:Aged; D017209:Apoptosis; D002462:Cell Membrane; D003110:Colonic Neoplasms / Q000276:immunology* / Q000503:physiopathology*; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D019169:Jurkat Cells; D008214:Lymphocytes; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D008875:Middle Aged; D014407:Tumor Cells, Cultured
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins