Role of Fas ligand expression in promoting escape from immune rejection ina spontaneous tumor model

Tumors escape immune-mediated rejection by a variety of mechanisms during t umor progression. The elucidation of these mechanisms in vivo suffers from a lack of suitable models of spontaneous tumor formation escaping active sp ecific immunotherapy (ASI). In a rat neu transgenic (rNeu-TG) mouse model o f spontaneous breast tumor formation, we showed that rNeu-TG mice developed late escape tumors despite the presence of a persistent rNeu-specific immu ne response after ASI. Cell suspensions derived from these escape tumors gr ew in vaccinated tumor-free mice, whereas injected spontaneous tumor cells were rejected. Escape tumors retained rNeu or MHC class I expression but si gnificantly upregulated pas (CD95, Apo-I) ligand. We further demonstrated t hat Fas-L an escape tumor cells correlated with apoptosis of infiltrating T lymphocytes. Thus, our results provide evidence that spontaneous breast tu mors upregulate Fas-L expression after vaccination that may promote tumor e scape in vivo after ASI. (C) 2001 Wiley-Liss, Inc.