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Determination of the Relative Potency of an Anti-TNF Monoclonal Antibody (mAb) by Neutralizing TNF Using an In Vitro Bioanalytical Method
Published on: September 16, 2017
Tumor necrosis factor, lymphotoxin and cancer
Marina S Drutskaya1, Grigory A Efimov, Andrey A Kruglov
1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia. marinadru@gmail.com
IUBMB Life
|February 16, 2010
Summary
Tumor necrosis factor (TNF) and lymphotoxins have dual roles in cancer, acting as both anti-tumor and pro-tumorigenic factors. Their complex signaling pathways influence host defense, inflammation, and immune system homeostasis, impacting cancer development and treatment.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Tumor necrosis factor (TNF) was initially identified as an anti-tumor agent but is now recognized for its broad roles in innate immunity and inflammation.
- Dysregulation of TNF signaling can lead to detrimental effects, contributing to treatment failures in oncology and influencing tumor-promoting activities.
- Anti-TNF therapies are effective in autoimmune diseases but carry risks such as immune suppression and potential lymphoma predisposition.
Purpose of the Study:
- To review the dual role of TNF and lymphotoxins in cancer.
- To explore the intricate signaling mechanisms of TNF and lymphotoxins through their receptors.
- To critically assess whether TNF and lymphotoxins are intrinsically anti-cancer or pro-tumorigenic.
Main Methods:
- Literature review of existing research on TNF and lymphotoxin signaling.
- Analysis of experimental models investigating the pro- and anti-tumorigenic effects of TNF.
- Examination of the role of lymphotoxin signaling pathways in immune system development and cancer.
Main Results:
- TNF exhibits context-dependent effects, acting as an anti-tumor factor in some settings and pro-tumorigenic in others, particularly via the TNF-TNFRp55 axis.
- Lymphotoxins (LTs) alpha and beta, signaling through TNFR I, TNFR II, and LTbetaR, are crucial for immune system homeostasis.
- Emerging evidence links the LTalpha/LTbeta-LTbetaR axis to cancer, highlighting its complex involvement.
Conclusions:
- The role of TNF and lymphotoxins in cancer is complex and multifaceted, with both beneficial and detrimental implications.
- Understanding the precise signaling pathways and cellular contexts is crucial for harnessing their therapeutic potential.
- Further research is needed to elucidate the net effect of these cytokines in tumorigenesis and to optimize anti-TNF/LT therapies.
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