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T cell-tumor cell: a fatal interaction?
1The Howard Hughes Medical Institute-National Institutes of Health Research Scholars Program, Bethesda MD 20814, USA.
Abstract:
Fas (Apo-1/CD95) is a cell-surface protein that is responsible for initiating a cascade of proteases (caspases) culminating in apoptotic cell death in a variety of cell types. The function of the Fas/FasL system in the dampening of immune responses to infectious agents through the autocrine deletion of activated T cells has been well documented. More recently, it has been proposed that tumor cells express FasL, presumably to avoid immune detection. In this review, we focus on the role of the interaction of Fas and FasL in the modulation of antitumor responses. We critically examine the evidence that FasL is expressed by tumor cells and explore alternative explanations for the observed phenomena in vitro and in vivo. By reviewing data that we have generated in our laboratory as well as reports from the literature, we will argue that the Fas/FasL system is a generalized mechanism used in an autocrine fashion to regulate cell survival and expansion in response to environmental and cellular cues. We propose that FasL expression by tumor cells, when present, is indicative of a perturbed balance in the control of proliferation while "immune privilege" is established by "suicide" of activated antitumor T cells, a form of activation-induced cell death.
Insights
The Fas/FasL system regulates cell death and survival. Tumor cells expressing Fas Ligand (FasL) may indicate uncontrolled proliferation and T cell deletion, establishing immune privilege.
Area of Science:
- Immunology
- Cell Biology
- Cancer Biology
Background:
- Fas (Apo-1/CD95) initiates apoptosis via caspase cascades.
- The Fas/FasL system is known to dampen immune responses by deleting activated T cells.
- Tumor cells are proposed to express FasL to evade immune surveillance.
Purpose of the Study:
- To review the role of Fas/FasL interactions in modulating antitumor responses.
- To critically evaluate evidence for FasL expression by tumor cells.
- To explore alternative explanations for observed FasL phenomena in vitro and in vivo.
Main Methods:
- Literature review of published data.
- Analysis of laboratory-generated data.
- Critical examination of in vitro and in vivo experimental findings.
Main Results:
- The Fas/FasL system acts as a general autocrine mechanism for regulating cell survival and expansion.
- Tumor cell FasL expression is not consistently proven and may have alternative explanations.
- Observed FasL expression in tumors suggests a disruption in proliferation control.
Conclusions:
- The Fas/FasL system is a fundamental regulator of cell fate.
- Tumor cell FasL expression is linked to dysregulated proliferation and immune evasion.
- Immune privilege in tumors can arise from activation-induced cell death of T cells.