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The multifaceted role of TRAIL signaling in cancer and immunity

Ludmila Cardoso Alves1, Nadia Corazza1, Olivier Micheau2

  • 1Institute of Pathology, University of Bern, Switzerland.

The FEBS Journal
|November 20, 2020
PubMed

Insights

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) can induce apoptosis but also nonapoptotic pathways in cancer and immune cells. This review explores TRAIL

Area of Science:

  • Immunology
  • Molecular Biology
  • Cancer Biology

Background:

  • TRAIL (TNF-related apoptosis-inducing ligand) is a TNF superfamily member.
  • TRAIL signaling induces apoptosis in tumor and infected cells.
  • TRAIL can also activate nonapoptotic pathways in cancer and immune cells.

Purpose of the Study:

  • To review current knowledge on noncanonical TRAIL signaling.
  • To explain biological outcomes of TRAIL signaling in immune and malignant cells.
  • To focus on TRAIL's role in natural killer (NK) cell function.

Main Methods:

  • Literature review of TRAIL signaling.
  • Analysis of molecular mechanisms.
  • Discussion of therapeutic implications.

Main Results:

  • TRAIL signaling has diverse biological outcomes beyond apoptosis.
  • NK cell function is significantly influenced by TRAIL.
  • Dissecting TRAIL's apoptotic vs. nonapoptotic switch presents technical challenges.

Conclusions:

  • Understanding noncanonical TRAIL signaling is crucial for cancer therapy.
  • Challenges exist in manipulating TRAIL therapeutically.
  • New approaches are needed to bypass difficulties in TRAIL pathway manipulation.
Keywords:
NK cellsTRAIL signalingapoptosiscancerimmune cell regulationnoncanonical TRAIL signaling

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