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The Janus Face of Death Receptor Signaling during Tumor immunoediting

期刊

FRONTIERS IN IMMUNOLOGY
卷 7, 期 -, 页码 -

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2016.00446

关键词

TNF-related apoptosis-inducing ligand (TRAIL); FAS (CD95); apoptosis; necroptosis; pro-survival signaling; immune surveillance; cancer

资金

  1. Science Foundation Ireland
  2. Irish Cancer Society (BCNI) [14/ICS/B3042]
  3. Irish Research Council [EPSPG/2015/91]
  4. Millennium Pilot Grant from NUI Galway
  5. Health Research Board [HRA-POR-2014-643]
  6. Health Research Board (HRB) [HRA-POR-2014-643] Funding Source: Health Research Board (HRB)
  7. Irish Research Council (IRC) [EPSPG/2015/91] Funding Source: Irish Research Council (IRC)
  8. Science Foundation Ireland (SFI) [14/ICS/B3042] Funding Source: Science Foundation Ireland (SFI)

向作者/读者索取更多资源

Cancer immune surveillance is essential for the inhibition of carcinogenesis. Malignantly transformed cells can be recognized by both the innate and adaptive immune systems through different mechanisms. Immune effector cells induce extrinsic cell death in the identified tumor cells by expressing death ligand cytokines of the tumor necrosis factor ligand family. However, some tumor cells can escape immune elimination and progress. Acquisition of resistance to the death ligand-induced apoptotic pathway can be obtained through cleavage of effector cell expressed death ligands into a poorly active form, mutations or silencing of the death receptors, or overexpression of decoy receptors and pro-survival proteins. Although the immune system is highly effective in the elimination of malignantly transformed cells, abnormal/dysfunctional death ligand signaling curbs its cytotoxicity. Moreover, DRs can also transmit pro-survival and pro-migratory signals. Consequently, dysfunctional death receptor-mediated apoptosis/necroptosis signaling does not only give a passive resistance against cell death but actively drives tumor cell motility, invasion, and contributes to consequent metastasis. This dual contribution of the death receptor signaling in both the early, elimination phase, and then in the late, escape phase of the tumor immunoediting process is discussed in this review. Death receptor agonists still hold potential for cancer therapy since they can execute the tumor-eliminating immune effector function even in the absence of activation of the immune system against the tumor. The opportunities and challenges of developing death receptor agonists into effective cancer therapeutics are also discussed.

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