Tumor-induced death of immune cells: its mechanisms and consequences

Seminars in Cancer Biology
T L Whiteside

Abstract

FasL is a death-inducing as well as pro-inflammatory molecule. The seemingly opposing consequences of Fas/FasL interactions appear to be dependent on the context of the tumor or tissue microenvironment. The term 'contextual' has been coined to describe cellular and molecular events that may be opposing, yet are mediated by the engagement of the same receptor-ligand pair. Because Fas is one of the death-inducing receptors, its ligand is dangerous. Hence, the availability of FasL for cross-linking of the receptor has to be extremely carefully regulated. Different levels of control appear to exist, some involving cell membrane-associated MMPs and others depending on cytokines released from neighboring cells. In tumors, which shape their microenvironment to make it unwelcome to immune effector cells, FasL is used to kill infiltrating cells without damage to the tumor, which develops multiple means of hiding/inhibiting the death pathway. On the other hand, in situations provoking inflammatory responses such as allograft rejection, infection, and tissue necrosis, FasL assumes the role of attractant for inflammatory cells. In these situations, FasL acts in conjunction with other cytokines, and its effects might be modified in the cont...Continue Reading

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