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Tumor-derived exosomes in the regulation of macrophage polarization

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Abstract

Background

This review focuses on exosomes derived from various cancer cells. The review discusses the possibility of differentiating macrophages in alternatively activated anti-inflammatory pro-tumorigenic M2 macrophage phenotypes and classically activated pro-inflammatory, anti-tumorigenic M1 macrophage phenotypes in the tumor microenvironment (TME). The review is divided into two main parts, as follows: (1) role of exosomes in alternatively activating M2-like macrophages-breast cancer-derived exosomes, hepatocellular carcinoma (HCC) cell-derived exosomes, lung cancer-derived exosomes, prostate cancer-derived exosomes, Oral squamous cell carcinoma (OSCC)—derived exosomes, epithelial ovarian cancer (EOC)—derived exosomes, Glioblastoma (GBM) cell-derived exosomes, and colorectal cancer-derived exosomes, (2) role of exosomes in classically activating M1-like macrophages, oral squamous cell carcinoma-derived exosomes, breast cancer-derived exosomes, Pancreatic-cancer derived modified exosomes, and colorectal cancer-derived exosomes, and (3) exosomes and antibody-dependent cellular cytotoxicity (ADCC). This review addresses the following subjects: (1) crosstalk between cancer-derived exosomes and recipient macrophages, (2) the role of cancer-derived exosome payload(s) in modulating macrophage fate of differentiation, and (3) intracellular signaling mechanisms in macrophages regarding the exosome’s payload(s) upon its uptake and regulation of the TME.

Evidence

Under the electron microscope, nanoscale exosomes appear as specialized membranous vesicles that emerge from the endocytic cellular compartments. Exosomes harbor proteins, growth factors, cytokines, lipids, miRNA, mRNA, and DNAs. Exosomes are released by many cell types, including reticulocytes, dendritic cells, B-lymphocytes, platelets, mast cells, and tumor cells. It is becoming clear that exosomes can impinge upon signal transduction pathways, serve as a mediator of signaling crosstalk, thereby regulating cell-to-cell wireless communications.

Conclusion

Based on the vesicular cargo, the molecular constituents, the exosomes have the potential to change the fate of macrophage phenotypes, either M1, classically activated macrophages, or M2, alternatively activated macrophages. In this review, we discuss and describe the ability of tumor-derived exosomes in the mechanism of macrophage activation and polarization.

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Acknowledgements

The authors are thankful to the Department of Biotechnology (DBT) for the Government of India sponsored Ramalingaswami Fellowship to MSB (BT/RLF/Re-entry/26/2013). The authors are thankful to the Department of Science and Technology (DST), Government of India for providing financial support under Early Career Research (ECR) Award (ECR/2016/00852) to MSB and American Heart Association support to KW. The authors also gratefully acknowledge the Indian Institute of Technology Indore (IITI) (MHRD) for providing facilities and other support.

Funding

The authors declare no funding support was received for this study.

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Author notes

  1. Mirza S. Baig, Anjali Roy and Sajjan Rajpoot contributed equally to this paper.

Authors and Affiliations

  1. Discipline of Biosciences and Biomedical Engineering (BSBE), Indian Institute of Technology Indore (IITI), Simrol, 453552, India

    Mirza S. Baig, Anjali Roy & Sajjan Rajpoot

  2. Department of Pathology, Immunology and Laboratory Medicine, Rutgers University-New Jersey Medical School, 185 South Orange Avenue, Newark, NJ, 07103, USA

    Dongfang Liu

  3. Center for Immunity and Inflammation, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, NJ, 07101, USA

    Dongfang Liu

  4. Max Planck Institute for Heart and Lung Research, Member of the German Center for Lung Research (DZL), Member of the Cardio-Pulmonary Institute (CPI), 61231, Bad Nauheim, Germany

    Rajkumar Savai

  5. Department of Internal Medicine, Member of the DZL, Member of CPI, Justus Liebig University, 350390, Giessen, Germany

    Rajkumar Savai

  6. Department of Biological Sciences, Middle East Technical University (METU), Ankara, 06800, Turkey

    Sreeparna Banerjee

  7. Laboratory of Oncology, Institute of Microbial Chemistry (BIKAKEN), 3-14-23 Kamiosaki, Shinagawa-ku, Tokyo, 141-0021, Japan

    Manabu Kawada & Tomokazu Ohishi

  8. Section of Animal Resources, Institute of Microbial Chemistry (BIKAKEN), 18-24 Miyamoto, Numazu-shi, Shizuoka, Numazu, 410-0301, Japan

    Manabu Kawada

  9. National Institute of Animal Biotechnology (NIAB), Hyderabad, 500032, India

    Syed M. Faisal

  10. Department of Biochemistry, All India Institute of Medical Sciences (AIIMS), Bhopal, 462020, India

    Rohit Saluja

  11. Discipline of Chemistry, Indian Institute of Technology Indore (IITI), Simrol, 453552, India

    Uzma Saqib

  12. Department of Pharmacology, The University of Illinois at Chicago, Chicago, IL, 60612, USA

    Kishore K. Wary

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  1. Mirza S. Baig
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  2. Anjali Roy
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Baig, M.S., Roy, A., Rajpoot, S. et al. Tumor-derived exosomes in the regulation of macrophage polarization. Inflamm. Res. 69, 435–451 (2020). https://doi.org/10.1007/s00011-020-01318-0

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  • DOI: https://doi.org/10.1007/s00011-020-01318-0

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