Antitumor effect of locally produced CD95 ligand

Abstract

Activation of the cell-surface antigen CD95 induces apoptosis of CD95-bearing tumor cells. In this study, we investigated the antitumor effect of locally produced CD95 ligand (CD95L) on CD95-negative tumor cells in vivo. Introduction of CD95L cDNA into murine tumor cells did not affect growth in vitro but caused rejection in vivo. Neutrophils were primarily responsible for this rejection. A CD8 T cell-mediated protective immunity against subsequent challenge with parental tumor cells was also elicited. These results provide evidence for the potential utility of CD95L in tumor eradication and also reveal a proinflammatory function of CD95L.

Antitumor effect of allogenic fibroblasts engineered to express Fas ligand (FasL)

“…Our unpublished data and reports in the literature 32 indicate that both BNL and CT26 are poorly immunogenic and express low levels of MHC class I antigens and no class II molecules. Thus, in accordance with previous studies, 21,27 our findings support the idea that immunity induced by FasL against tumors seems not to depend on the immunogenicity of the malignant cells.…”

“…In contrast, mice treated with BNL cells mixed with PA317/Contr exhibited progressive growth of neoplastic cells with formation of a tumor nodule surrounded by only a mild inflammatory reaction. This observation, which is similar to observations in previous reports using FasL-expressing tumor cells, 21 suggests that activation of neutrophils is a basic mechanism involved in tumor elimination in the system utilized in the present work.…”

“…22 Introduction of human or mouse FasL cDNA into murine tumor cells did not affect tumor growth in vitro but caused rejection of the tumor by infiltrating neutrophils with subsequent induction of tumorspecific protective immunity. 21 More recent data indicate that adenovirus-mediated gene transfer of mouse FasL induced tumor regression in animal models implanted with Fas-positive and -negative tumor cells. 27 In the light of the above data we decided to study whether allogenic fibroblasts engineered to express FasL are able to abolish tumorigenicity and induce tumorspecific protective immunity.…”

“…[17][18][19][20] On the other hand, it was shown that the presence of FasL can involve destruction of FasL-bearing cells. First, Seino et al 21 showed that introduction of FasL cDNA into murine tumor cells did not affect growth in vitro but caused rejection in vivo. Further, Kang et al 22 reported that transplantation of islets of Langerhans infected with an adenoviral vector containing FasL into allogenic diabetic hosts underwent accelerated rejection.…”

The influence of CD95L expression on tumor rejection in mice

“…Various studies have shown that the overexpression of CD95L in murine tumor cells resistant to CD95-mediated apoptosis did not affect growth in vitro, but caused rejection, possibly by neutrophils, in vivo [26][27][28][29][30]. CD8 + T cellmediated protective immunity against subsequent challenge with the parental tumor cells was elicited.…”