Induction of antitumor immunity with Fas/APO-1 ligand (CD95L)-transfected neuroblastoma Neuro-2a cells

Fas/Apo-1 (CD95)-Fas ligand (FasL) system has been implicated in the suppre ssion and stimulation of immune responses. We examined the induction of ant itumor immunity with neuroblastoma Neuro-2a cells transfected with Fast cDN A (Neuro-2a+FasL), Neuro-2a+FasL cells expressed FasL on the cell surface a nd secreted soluble, Fast. Histologic and flow cytometric analyses revealed that Neuro-2a+FasL cells caused neutrophils to infiltrate into the injecte d site, resulting in strong inflammation, Neutrophil infiltration was inhib ited by treatment with anti-FasL mAb and did not occur in Fas-deficient lpr mice. Normal syngeneic mice rejected Neuro-2a+FasL cells after the inflamm ation and acquired tumor-specific protective immunity. CD8(+) T cells were responsible for the antitumor immunity. Neuro-2a+FasL cells formed tumors a fter far longer latency compared with mock-transfected Neuro-2a+Neo cells i n nude mice, and immune competent mice rejected Neuro-2a cells but not sarc oma S713a cells when they were injected with Neuro-2a+FasL cells in a mixtu re. These results suggest that neutrophils attracted through the Fas-FasL s ystem may impair tumor cells by inflammation at the initial step, followed by development of CD8(+) T: cell-dependent tumor-specific antitumor:immunit y, leading to complete eradication of tumor cells, Importantly; the treatme nt with Neuro-2a+FasL cells exhibited therapeutic efficacy against growing tumors.