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Stem Cells. 2017 May;35(5):1123-1130. doi: 10.1002/stem.2596. Epub 2017 Mar 28.

Concise Review: An (Im)Penetrable Shield: How the Tumor Microenvironment Protects Cancer Stem Cells.

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The Research Institute, Columbus, Ohio, USA.
Medical Scientist Training Program, Columbus, Ohio, USA.
Department of Medical and Surgical Sciences of Children and Adults, University of Modena and Reggio Emilia, Modena, Italy.
Departments of Pediatrics and Medicine, Nationwide Children's Hospital, Columbus, Ohio, USA.
The Division of Hematology/Oncology/BMT, Ohio State University College of Medicine, Columbus, Ohio, USA.


Cancer stem cells (CSCs) are defined by their unlimited self-renewal ability and their capacity to initiate and maintain malignancy, traits that are not found in most cells that comprise the tumor. Although current cancer treatments successfully reduce tumor burden, the tumor will likely recur unless CSCs are effectively eradicated. This challenge is made greater by the protective impact of the tumor microenvironment (TME), consisting of infiltrating immune cells, endothelial cells, extracellular matrix, and signaling molecules. The TME acts as a therapeutic barrier through immunosuppressive, and thereby tumor-promoting, actions. These factors, outside of the cancer cell lineage, work in concert to shelter CSCs from both the body's intrinsic anticancer immunity and pharmaceutical interventions to maintain cancer growth. Emerging therapies aimed at the TME offer a promising new tool in breaking through this shield to target the CSCs, yet definitive treatments remain unrealized. In this review, we summarize the mechanisms by which CSCs are protected by the TME and current efforts to overcome these barriers. Stem Cells 2017;35:1123-1130.


Cancer stem cells; Cell interactions; Microenvironment; Neoplastic stem cell biology; Stem cell-microenvironment interactions

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