Inhibition of fas-mediated apoptosis.

Submitted March 20, 2006

Abstract

CD95/Fas belongs to a subset of death receptors within the TNF superfamily that
transmit an apoptotic signal upon ligand binding. Inhibition of Fas by altered expression
of endogenous proteins can contribute to tumor growth by evasion of the Fas apoptotic
signal. It is probable that cancers developing from immune-privileged tissues expressing
Fas ligand (FasL) also express apoptotic inhibitors providing protection from neighboring
cells. Glial cells express FasL that facilitates elimination of neuron-damaging T-cells in
the brain. Tumors arising from glial cells are often resistant to Fas, although the receptor
is expressed at normal levels. Gliomas are often unresponsive to chemotherapy or
treatment with ionizing radiation, likely because of a deficiency or block to apoptosis.
The high expression of the Fas inhibitor Lifeguard in cultured glioblastoma cells suggests
a mechanism that aids in tumor immune evasion.