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Chronic inflammation and cancer: suppressing the suppressors

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Abstract

Chronic inflammation typical to various chronic diseases is associated with immunosuppression, mediated primarily by immature myeloid-derived suppressor cells (MDSCs). A variety of factors induce MDSC differentiation arrest, thus manipulating the host’s immune function and suppressing the innate and adaptive immune systems, as reflected by their impaired status associated with down-regulated expression of the CD247 molecule. Such chronic inflammation-induced immunosuppressive features are also found in many tumors, generating tumor micro- and macro-environments that act as critical barriers to effective anti-tumor responses and therapies. This knowledge offers new and novel candidate immune targets for therapeutic interventions, in combination with more conventional approaches as chemotherapy, radiotherapy, and cancer cell targeted therapy. Therapeutic manipulation of chronic inflammation during cancer development is likely to enhance efficacy of treatments such as vaccinations, and adoptive T cell transfer, thus switching the chronic pro-cancer inflammatory environments into an anti-cancer milieu. Based on the functional relevance of immune networking in tumors, it is advantageous to merge monitoring immune biomarkers into the traditional patient’s categorization and treatment regiments, which will provide new prognostic and/or predictive tools to clinical practice. A better identification of environmental and tumor-specific inflammatory mechanisms will allow directing the clinical management of cancer toward a more personalized medicine.

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Acknowledgments

We gratefully acknowledge the support of the Society of Research Associates of the Lautenberg Center, the Concern Foundation of Los Angeles, and the Harold B. Abramson Chair in Immunology. This study was supported by the Israel Science foundation (ISF), the Israeli Ministry of Health, the Joint German-Israeli Research Program (DKFZ-MOST), the Israel Cancer Research Fund (ICRF), and the United States-Israel Binational Science Foundation (BSF) and by the Joseph and Matilda Melnick Funds. We thank Dr. Lynn Wang for reading and commenting on the manuscript.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Faculty of Medicine, Israel-Canada Medical Research Institute, The Lautenberg Center for General and Tumor Immunology, The Hebrew University, POB: 12272, 91120, Jerusalem, Israel

    Michal Baniyash, Moshe Sade-Feldman & Julia Kanterman

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  1. Michal Baniyash
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  2. Moshe Sade-Feldman
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  3. Julia Kanterman
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Correspondence to Michal Baniyash.

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Moshe Sade-Feldman and Julia Kanterman contributed equally to this review.

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Baniyash, M., Sade-Feldman, M. & Kanterman, J. Chronic inflammation and cancer: suppressing the suppressors. Cancer Immunol Immunother 63, 11–20 (2014). https://doi.org/10.1007/s00262-013-1468-9

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