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 serve s as a potential mechanism to inhibit host immune function by inducing apop tosis of host lymphocytes, Membrane-bound FasL can be cleaved and released as a soluble mediator (sFasL), which may spread the apoptosis induction eff ect. Our study examined whether colon adenocarcinoma cells release sFasL, a nd induce apoptosis of host lymphocytes without direct cell-cell contact. I n 12 consecutive patients with colon adenocarcinoma mFasL was identified in the tumours, sFasL was measured in the sera and apoptosis identified in tu mour-infiltrating and peripheral blood lymphocytes. To analyse the function of sFasL, colon cancer cells were primarily cultured; sFasL was isolated f rom supernatants, measured, incubated with Fas-bearing Jurkat cells, and th e resulting apoptosis was analysed. Serum levels of sFasL were significantl y elevated in ail colon cancer patients with mFasL expression in tumour tis sues (n = 8). In these patients, the number of apoptotic lymphocytes was si gnificantly increased within tumour and peripheral blood, Furthermore, sFas L was present in the corresponding supernatants and induced apoptosis of Ju rkat cells in a close-dependent manner. These findings suggest that mFasL-p ositive colon cancer cells release sFasL, and thus may induce apoptosis of host lymphocytes as a potential mechanism for immune evasion. (C) 2001 Canc er Research Campaign http://www.bjcancer.com.