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Myeloid-derived suppressor cells as intruders and targets: clinical implications in cancer therapy

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Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Chronic inflammation, typical of various diseases including cancer, is a “silent bomb within the body,” leading to complications that are only evident in most cases upon their appearance, when disease is already deteriorated. Chronic inflammation is associated with accumulation of myeloid-derived suppressor cells (MDSCs), which lead to immunosuppression. MDSCs have numerous harmful effects as they support tumor initiation, tumor growth and spreading, which in turn, perpetuate the inflammatory and suppressive conditions, thus preventing anticancer responses. As the concept of the immune system combating many types of tumors was revived in recent years, immunotherapy has dramatically changed the view of cancer treatment, and numerous novel therapies have been developed and approved by the FDA. However, cumulative clinical data point at very limited success rates. It is most likely that the developing chronic inflammation and MDSC-induced immunosuppression interfere with responses to such treatments and hence are major obstacles in achieving higher response rates to immune-based therapies. Moreover, chemotherapies were shown to have adverse immunoregulatory effects, enhancing or decreasing MDSC levels and activity, thus affecting treatment success. Therefore, therapeutic manipulations of chronic inflammation and MDSCs during cancer development are likely to enhance efficacy of immune- and chemo-based treatments, switching chronic pro-cancer inflammatory environments to an anticancerous milieu. Based on the functional relevance of immune networking in tumors, it is critical to merge monitoring immune system biomarkers into the traditional patient’s categorization and treatment regimens. This will provide new tools for clinical practice, allowing appropriate management of cancer patients toward a better-personalized medicine.

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Abbreviations

ARG-1:

Arginase-1

BM:

Bone marrow

CP:

Cyclophosphamide

CRC:

Colorectal cancer

DCs:

Dendritic cells

IBD:

Inflammatory bowel diseases

iNOS:

Inducible nitric oxide synthase

MDSCs:

Myeloid-derived suppressor cells

NO:

Nitric oxide

PFS:

Progression-free survival

RAGE:

Receptor for advanced glycation end products

ROS:

Reactive oxygen species

TLR:

Toll-like receptor

Tregs:

Regulatory T cells

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Acknowledgments

I 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. Thanks to Drs. Lynn Wang and Leonor Daniel and Yaron Meirow for reviewing the manuscript and my team Julia Kanterman-Rifman, Yaron Meirow, Kerem Ben-Meir, Hadas Ashkenazi, Nira Twaik, Hana Vardi, Drs. Lynn Wang, Leonor Daniel, Ivan Mikula and my former student Dr. Moshe Sade-Feldman for forming the research and clinical basis for this review.

This study was supported by the Israel Science Foundation (ISF), the Israeli Ministry of Health, the Joint German-Israeli Research Program (DKFZ), the Israel Cancer Research Fund (ICRF), the China-Israel Binational Science Foundation (NSFC-ISF), The Nofar program of the Chief Scientist Office (OCS), Israel and by the Joseph and Matilda Melnick Funds.

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  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

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Correspondence to Michal Baniyash.

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Baniyash, M. Myeloid-derived suppressor cells as intruders and targets: clinical implications in cancer therapy. Cancer Immunol Immunother 65, 857–867 (2016). https://doi.org/10.1007/s00262-016-1849-y

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