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TNFα and Immune Checkpoint Inhibition: Friend or Foe for Lung Cancer?

Tijdschriftbijdrage - Review Artikel

Tumor necrosis factor-alpha (TNFα) can bind two distinct receptors (TNFR1/2). The transmembrane form (tmTNFα) preferentially binds to TNFR2. Upon tmTNFα cleavage by the TNF-alpha-converting enzyme (TACE), its soluble (sTNFα) form is released with higher affinity for TNFR1. This assortment empowers TNFα with a plethora of opposing roles in the processes of tumor cell survival (and apoptosis) and anti-tumor immune stimulation (and suppression), in addition to angiogenesis and metastases. Its functions and biomarker potential to predict cancer progression and response to immunotherapy are reviewed here, with a focus on lung cancer. By mining existing sequencing data, we further demonstrate that the expression levels of TNF and TACE are significantly decreased in lung adenocarcinoma patients, while the TNFR1/TNFR2 balance are increased. We conclude that the biomarker potential of TNFα alone will most likely not provide conclusive findings, but that TACE could have a key role along with the delicate balance of sTNFα/tmTNFα as well as TNFR1/TNFR2, hence stressing the importance of more research into the potential of rationalized treatments that combine TNFα pathway modulators with immunotherapy for lung cancer patients.
Tijdschrift: International Journal of Molecular Sciences
ISSN: 1661-6596
Issue: 16
Volume: 22
Jaar van publicatie:2021
Trefwoorden:lung cancer, Immunotherapy, immune, TNFR1, TNFR2
  • ORCID: /0000-0003-1482-1742/work/121062160
  • ORCID: /0000-0002-4831-002X/work/121054914
  • WoS Id: 000689147100001
  • PubMed Id: 34445397
  • Scopus Id: 85112393602
  • DOI: https://doi.org/10.3390/ijms22168691
BOF-keylabel:ja
IOF-keylabel:ja
BOF-publication weight:1
Auteurs:Regional
Authors from:Higher Education
Toegankelijkheid:Open