Review Article | Published:

NF-κB: linking inflammation and immunity to cancer development and progression

Nature Reviews Immunology volume 5, pages 749759 (2005) | Download Citation



There has been much effort recently to probe the long-recognized relationship between the pathological processes of infection, inflammation and cancer. For example, epidemiological studies have shown that 15% of human deaths from cancer are associated with chronic viral or bacterial infections. This Review focuses on the molecular mechanisms that connect infection, inflammation and cancer, and it puts forward the hypothesis that activation of nuclear factor-κB (NF-κB) by the classical, IKK-β (inhibitor-of-NF-κB kinase-β)-dependent pathway is a crucial mediator of inflammation-induced tumour growth and progression, as well as an important modulator of tumour surveillance and rejection.

Key points

  • Chronic inflammation has been suspected to be an important cause of tumour development. Nuclear factor-κB (NF-κB) activation can contribute to inflammation and tumorigenesis during tumour promotion and progression.

  • In several animal models of inflammation-associated cancer, NF-κB activation prevents the apoptosis of cells that are destined to become tumorigenic by upregulating the expression of anti-apoptotic genes, such as those encoding BCL-XL (B-cell lymphoma XL), BFL1 (a BCL-2-related protein) and GADD45β (growth arrest and DNA-damage-inducible 45β).

  • In myeloid cells, NF-κB activation leads to the transcription of genes encoding growth and survival factors that can promote the proliferation of tumour cells.

  • In a chemically induced model of liver cancer, inhibition of NF-κB activation leads to increased tumour growth, through increased initial death of hepatocytes and increased compensatory proliferation, which is promoted by adjacent Kupffer cells.

  • Serine proteases and other factors that are released by necrotic cells seem to be important stimulators of inflammatory cells, which in turn promote tumour growth.

  • Tumour-necrosis factor and interleukin-6 are important mediators during inflammation and tumour promotion, leading to activation of NF-κB and thereby suppression of cell death and stimulation of cell proliferation.

  • Inhibition of NF-κB during cancer therapy could be a useful strategy, because it would be effective in different cell types. In malignant cells, inhibition would increase susceptibility to apoptosis-inducing agents, and in inflammatory cells, it would inhibit the expression of growth and survival factors.

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The authors thank J. Jenkins for help with manuscript preparation.

Author information


  1. Laboratory of Gene Regulation and Signal Transduction, University of California at San Diego School of Medicine, Department of Pharmacology, 9500 Gilman Drive, La Jolla, California 92093-0723, USA.

    • Michael Karin
  2. II Medizinische Klinik Klinikum Rechts der Isar, Techinische Universitat München, Ismaningerstrasse 22, 81675 München, Germany.

    • Florian R. Greten


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Correspondence to Michael Karin.



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A drug that suppresses inflammation in a manner that is similar to that of steroids but that has a chemical structure and side-effects that are different from those of steroids. These drugs usually inhibit cyclooxygenase-2.


An important component of the tumour microenvironment. These cells differentiate from circulating blood monocytes that have infiltrated tumours. These cells can have positive or negative effects on tumorigenesis (that is, tumour promotion or immunosurveillance, respectively).


Owing to disruption of the gene encoding MDR2 (multidrug resistance 2; also known as P-glycoprotein), this mouse strain is characterized by cholangitis and cholestatic hepatitis, leading to hepatocellular carcinoma.


A mouse model of skin cancer using 7,12-dimethylbenz(a)-anthracene (DMBA) for initiation and 12-O-tetradecanoyl phorbol 13-acetate (TPA) as a tumour promoter.


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