The Dark Side of the Force: When the Immune System Is the Fuel of Tumor Onset

Our plain-English summary of The Dark Side of the Force: When the Immune System Is the Fuel of Tumor Onset, by E. Digifico, S. Balinzo, C. Belgiovine (International Journal of Molecular Sciences, 2021).

The study

• Authors: E. Digifico, S. Balinzo, C. Belgiovine
• Journal: International Journal of Molecular Sciences
• Published: 2021;22(3)
• Type of article: Review
• Cited by: 9 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Nowadays, it is well accepted that inflammation is a critical player in cancer, being, in most cases, the main character of the process. Different types of tumor arise from sites of infection or chronic inflammation. This non-resolving inflammation is responsible for tumor development at different levels: it promotes tumor initiation, as well as tumor progression, stimulating both tumor growth and metastasis. Environmental factors, lifestyle and infections are the three main triggers of chronic immune activation that promote or increase the risk of many different cancers. In this review, we focus our attention on tumor onset; in particular, we summarize the knowledge about the cause and the mechanisms behind the inflammation-driven cancer development.

In plain English

This review summarized earlier published research on how long-lasting (chronic) inflammation may contribute to the start of cancer. The authors grouped the triggers as environmental factors (tobacco smoke, ultraviolet light, asbestos fibers), lifestyle (Western diet and alcohol) and infections (including Helicobacter pylori, hepatitis B and C viruses, HIV and certain parasites). They wrote that breast implant-associated lymphoma seems to be caused by infection and chronic inflammation. On asbestos, it described malignant mesothelioma as one of the clearest examples of a tumor arising from decades-long inflammation. It described inhaled fibers as causing inflammation that does not resolve because the fibers cannot be broken down. It cited other researchers' reports of more DNA double-strand breaks in the blood of workers exposed to asbestos at work, of asbestos activating an immune-cell inflammation sensor called the NLRP3 inflammasome, and of later tumor onset and fewer mesotheliomas in asbestos-exposed mice lacking part of this sensor. The authors concluded that several tumors are associated with chronic inflammation from external agents, lifestyle habits or infections, and that some of these tumors could be avoided through prevention.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review of published research (no new data collected by the authors)
• Who was studied: No study population of its own; the review summarized earlier laboratory, animal and human studies on inflammation and cancer
• Exposure: Triggers of chronic inflammation: tobacco smoke, e-cigarettes, ultraviolet light, asbestos fibers and naturally occurring asbestos, Western diet and alcohol, and infections (H. pylori, hepatitis B and C, HIV, parasites). The review also described breast implant-associated lymphoma as seeming to be caused by infection and chronic inflammation. Asbestos fiber types were not named.
• Main results:
  • The review stated that breast implant-associated anaplastic large cell lymphoma seems to be caused by pathogen infection and chronic inflammation.
  • The review described malignant mesothelioma as one of the clearest examples of a tumor arising from chronic, decades-long inflammation.
  • The review described inhaled asbestos fibers as causing inflammation that does not resolve because the fibers cannot be broken down.
  • The review cited an earlier study (Marczynski et al.) reporting a higher incidence of DNA double-strand breaks in the blood of workers exposed to asbestos at work.
  • The review cited earlier studies (Yang et al.) reporting that asbestos can cause mesothelial cells to die by necrosis and to release HMGB1.
  • The review cited earlier studies reporting that asbestos fibers can directly activate the NLRP3 inflammasome in innate immune cells.
  • The review cited an earlier study (Hillegass et al.) in which the increase in these inflammatory signals was blocked by the drug Anakinra, both in the laboratory and in animals.
  • The review cited an animal study (Kadariya et al.) reporting delayed tumor onset and reduced mesothelioma incidence in inflammasome-deficient mice, compared with normal (wild-type) mice chronically exposed to asbestos.
  • The review stated that the wide variety of gene mutations found in malignant pleural mesothelioma indicates there are no specific driver mutations.
• The authors' conclusion: The authors concluded that several tumors are associated with chronic inflammation arising from external agents, lifestyle habits or infectious diseases, and that some of these tumors could be avoided through prevention. Citing the Kadariya et al. mouse study, they wrote that the link between inflammation and mesothelioma provides a rationale for inflammation-targeting therapies in mesothelioma patients and for chemoprevention aimed at IL-1 beta and IL-1 receptor signaling in asbestos-exposed people.

Topics

Medical terms in this study, explained in our Lexicon: Inflammation, Chronic Inflammation, Metastasis.

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