Immunology in the clinic review series; focus on cancer: multiple roles for the immune system in oncogene addiction

Authors

  • P. Bachireddy,

    1. Department of Medicine, Brigham and Women's Hospital/Harvard Medical School, Boston, MA
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    • These authors contributed equally to this manuscript.

  • K. Rakhra,

    1. Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, Stanford, CA, USA
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    • These authors contributed equally to this manuscript.

  • D. W. Felsher

    Corresponding author
    1. Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, Stanford, CA, USA
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D. Felsher, Division of Oncology, Departments of Medicine and Pathology, Stanford University, Stanford, CA, USA. E-mail: dfelsher@stanford.edu

Abstract

OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIES

Metabolic Diseases, Host Responses, Allergies, Autoinflammatory Diseases, Type 1 diabetes and viruses.

Summary

Despite complex genomic and epigenetic abnormalities, many cancers are irrevocably dependent on an initiating oncogenic lesion whose restoration to a normal physiological activation can elicit a dramatic and sudden reversal of their neoplastic properties. This phenomenon of the reversal of tumorigenesis has been described as oncogene addiction. Oncogene addiction had been thought to occur largely through tumour cell-autonomous mechanisms such as proliferative arrest, apoptosis, differentiation and cellular senescence. However, the immune system plays an integral role in almost every aspect of tumorigenesis, including tumour initiation, prevention and progression as well as the response to therapeutics. Here we highlight more recent evidence suggesting that oncogene addiction may be integrally dependent upon host immune-mediated mechanisms, including specific immune effectors and cytokines that regulate tumour cell senescence and tumour-associated angiogenesis. Hence, the host immune system is essential to oncogene addiction.

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