Apoptosis Induced in T Cells by Human Neuroblastoma Cells: Role of Fas Ligand

Abstract

The CD95/CD95L (Fas/Fas ligand) receptor/ligand system plays an important role in regulation of cell survival and induction of a programmed cell death. It is also involved in regulation of effector phase of T and NK cell cytotoxicity, establishment of immune privilege sites, and tumor escape from immune recognition. In this study, we assessed expression of CD95L in tumors obtained from patients with neuroblastoma (NB) and in established NB cell lines. We measured the presence of intratumoral T cell infiltrates and T cell survival in tumor tissue samples. High levels of apoptosis were observed in tumor-associated lymphocytes as well as in Jurkat T cells cocultured with NB cells in vitro. T cell death was reduced after treatment of NB cells (in vitro) with antibody to FAS ligand (FasL). Overall, our data suggest that NB-induced apoptosis of Fas-sensitive Jurkat T cells is mediated by functional FasL expressed on NB and Fas/FasL interaction may be responsible for the elimination of T cells in the NB microenvironment.

Apoptosis and proliferation of acinar and islet cells in chronic pancreatitis: evidence for differential cell loss mediating preservation of islet function

“…24 Fas/Fas ligand binding usually induces apoptosis within the Fas expressing cells. 25 This suggests that pancreatic islet cells must possess an additional mechanism for inhibiting "self-induced" Fas/ Fas ligand triggered apoptosis. Current evidence suggests that the extracellular domain of the Fas ligand molecule is cleaved from expressing cells by a metalloproteinase dependent process to yield a product that is released from the membrane.…”

Myc pathways provoking cell suicide and cancer

“…This therefore suggests the Myc field would be well-served to look at the other side of the coin, where precancerous Myc-expressing cells would express regulators that specifically target immune cells for destruction. Indeed, MYCN-amplified neuroblastoma has been shown to express high levels of FasL (Shurin et al, 1998;Chen et al, 1999;Takamizawa et al, 2000). Clearly, direct genetic tests of Myc and immune privilege are now warranted.…”

Human Neuroblastoma Cells Trigger an Immunosuppressive Program in Monocytes by Stimulating Soluble HLA-G Release

“…Among them, immunotherapy has attracted interest, but its success may be limited by several mechanism adopted by neuroblastoma cells to evade the control of the immune system (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14).…”