Review Article

Harnessing nanomedicine to overcome the immunosuppressive tumor microenvironment

Authors: Bo Sun1, Hyesun Hyun2,3, Lian-tao Li4,5, Andrew Z Wang2,3
1 Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, AZ 85721, USA
2 Laboratory of Nano and Translational Medicine, Carolina Center for Cancer Nanotechnology Excellence, Carolina Institute of Nanomedicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
3 Department of Radiation Oncology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
4 Cancer Institute, Xuzhou Medical University, Xuzhou 221004, China
5 Department of Radiation Oncology, Affiliated Hospital of Xuzhou Medical University, Xuzhou 221004, China
Correspondence to: Andrew Z Wang:,
DOI: 10.1038/s41401-020-0424-4
Received: 12 February 2020
Accepted: 20 April 2020
Advance online: 18 May 2020


Cancer immunotherapy has received extensive attention due to its ability to activate the innate or adaptive immune systems of patients to combat tumors. Despite a few clinical successes, further endeavors are still needed to tackle unresolved issues, including limited response rates, development of resistance, and immune-related toxicities. Accumulating evidence has pinpointed the tumor microenvironment (TME) as one of the major obstacles in cancer immunotherapy due to its detrimental impacts on tumor-infiltrating immune cells. Nanomedicine has been battling with the TME in the past several decades, and the experience obtained could be exploited to improve current paradigms of immunotherapy. Here, we discuss the metabolic features of the TME and its influence on different types of immune cells. The recent progress in nanoenabled cancer immunotherapy has been summarized with a highlight on the modulation of immune cells, tumor stroma, cytokines and enzymes to reverse the immunosuppressive TME.
Keywords: cancer immunotherapy; tumor microenvironment; immunosuppression; immune cells; cytokines; enzymes; nanomedicine

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