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

Thomas Benoot1, Elisa Piccioni1, Kirsten De Ridder1

  • 1Laboratory for Molecular and Cellular Therapy, Department Biomedical Science, Vrije Universiteit Brussel (VUB), Laarbeeklaan 103, 1090 Brussels, Belgium.

International Journal of Molecular Sciences
|August 27, 2021
PubMed

Insights

Tumor necrosis factor-alpha (TNFα) plays dual roles in cancer. While TNFα alone may not be a definitive biomarker, its pathway, particularly TACE, TNFR1, and TNFR2, offers potential for lung cancer treatment strategies.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Tumor necrosis factor-alpha (TNFα) interacts with TNFR1 and TNFR2.
  • The balance between transmembrane (tmTNFα) and soluble (sTNFα) forms, influenced by TACE, dictates receptor binding and biological outcomes.
  • TNFα signaling is implicated in tumor survival, apoptosis, immune response, angiogenesis, and metastasis.

Purpose of the Study:

  • To review the functions and biomarker potential of TNFα in cancer progression and immunotherapy response, focusing on lung cancer.
  • To investigate the expression levels of TNFα pathway components in lung adenocarcinoma.
  • To explore the potential of targeting the TNFα pathway for lung cancer treatment.

Main Methods:

  • Literature review of TNFα functions and biomarker potential in cancer.
  • Bioinformatic analysis of existing sequencing data for TNF, TACE, TNFR1, and TNFR2 expression in lung adenocarcinoma.
  • Analysis of the balance between sTNFα and tmTNFα, and TNFR1/TNFR2 expression.

Main Results:

  • Expression of TNF and TACE was significantly decreased in lung adenocarcinoma patients.
  • The balance of TNFR1/TNFR2 expression was increased in lung adenocarcinoma patients.
  • TNFα's role in cancer is complex, with opposing effects on tumor cell fate and immune responses.

Conclusions:

  • TNFα alone is unlikely to be a conclusive biomarker for cancer progression or immunotherapy response.
  • TACE, along with the sTNFα/tmTNFα and TNFR1/TNFR2 balance, may hold significant biomarker and therapeutic potential.
  • Further research is crucial for developing rationalized combination treatments involving TNFα pathway modulators and immunotherapy for lung cancer.
Keywords:
TNFR1TNFR2TNFαimmune checkpoint inhibition (Min. 5–Max. 8)immunotherapylung cancer

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