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Resolution of Gastric Cancer-Promoting Inflammation: A Novel Strategy for Anti-cancer Therapy

  • M. Blanca Piazuelo
  • Rachel P. Riechelmann
  • Keith T. Wilson
  • Holly M. Scott AlgoodEmail author
Chapter
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 421)

Abstract

The connection between inflammation and cancer was initially recognized by Rudolf Virchow in the nineteenth century. During the last decades, a large body of evidence has provided support to his hypothesis, and now inflammation is recognized as one of the hallmarks of cancer, both in etiopathogenesis and ongoing tumor growth. Infection with the pathogen Helicobacter pylori is the primary causal factor in 90% of gastric cancer (GC) cases. As we increase our understanding of how chronic inflammation develops in the stomach and contributes to carcinogenesis, there is increasing interest in targeting cancer-promoting inflammation as a strategy to treat GC. Moreover, once cancer develops and anti-cancer immune responses are suppressed, there is evidence of a substantial shift in the microenvironment and new targets for immune therapy emerge. In this chapter, we provide insight into inflammation-related factors, including T lymphocytes, macrophages, pro-inflammatory chemokines, and cytokines, which promote H. pylori-associated GC initiation and growth. While intervening with chronic inflammation is not a new practice in rheumatology or gastroenterology, this approach has not been fully explored for its potential to prevent carcinogenesis or to contribute to the treatment of GC. This review highlights current and possible strategies for therapeutic intervention including (i) targeting pro-inflammatory mediators, (ii) targeting growth factors and pathways involved in angiogenesis in the gastric tumor microenvironment, and (iii) enhancing anti-tumor immunity. In addition, we highlight a significant number of clinical trials and discuss the importance of individual tumor characterization toward offering personalized immune-related therapy.

Keywords

Immunotherapy Gastric cancer Helicobacter pylori Inflammation Immune modulation 

Notes

Acknowledgements

This work was supported by U. S. National Institutes of Health (NIH) grants R01AT004821, R01CA190612, P01CA116087, P01CA028842; Office of Medical Research, Veterans Affairs Merit Review grants IBX000915A(to H.M.S.A.) and I01BX001453(to K.T.W.); and Vanderbilt University Digestive Disease Research Center supported by NIH grant P30DK058404.

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Copyright information

© This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2019

Authors and Affiliations

  • M. Blanca Piazuelo
    • 1
  • Rachel P. Riechelmann
    • 2
  • Keith T. Wilson
    • 3
  • Holly M. Scott Algood
    • 3
    Email author
  1. 1.Department of Medicine, Vanderbilt Center for Mucosal Inflammation and CancerVanderbilt University Medical CenterNashvilleUSA
  2. 2.Department of Clinical OncologyAC Camargo Cancer CenterSao PauloBrazil
  3. 3.Tennessee Valley Healthcare System, Department of Veterans Affairs, Department of Medicine, Department of Pathology, Microbiology and Immunology, Vanderbilt Center for Mucosal Inflammation and Cancer, Vanderbilt Institute of Infection, Immunity and Inflammation (VI4), Vanderbilt Ingram Cancer CenterVanderbilt University Medical CenterNashvilleUSA

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