The role of death receptor ligands in shaping tumor microenvironment

Immunol Invest. 2007;36(1):25-46. doi: 10.1080/08820130600991893.

Abstract

Death receptor ligands (FasL, TRAIL) activate apoptosis in cells expressing the cognate receptors. Evidence suggests that these ligands also deliver pro-inflammatory signals. In the tumor microenvironment, "Fas counterattack" mounted by tumors against immune cells is mediated by tumor-associated FasL. But death ligands crosslinking their receptors also induce inhibition of apoptosis and activation of the transcription factor, NFkappaB, with a subsequent burst of pro-inflammatory cytokine production and tumor growth promotion. NFkappaB, a key link between inflammation and cancer, regulates dual activities of death ligands, depending on molecular signals in the tumor microenvironment. This paper focuses on death ligands as an example of the extensive repertoire of strategies devised by tumors for escape from immune control.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Fas Ligand Protein / metabolism*
  • Immunity, Cellular
  • Inflammation / metabolism
  • Models, Immunological
  • Neoplasms / immunology
  • Neoplasms / metabolism*
  • Signal Transduction*
  • TNF-Related Apoptosis-Inducing Ligand / metabolism*
  • Tumor Escape*

Substances

  • Antineoplastic Agents
  • Fas Ligand Protein
  • TNF-Related Apoptosis-Inducing Ligand