Immunosuppressive cells in tumor immune escape and metastasis

J Mol Med (Berl). 2016 May;94(5):509-22. doi: 10.1007/s00109-015-1376-x. Epub 2015 Dec 22.


Tumor immune escape and the initiation of metastasis are critical steps in malignant progression of tumors and have been implicated in the failure of some clinical cancer immunotherapy. Tumors develop numerous strategies to escape immune surveillance or metastasize: Tumors not only modulate the recruitment and expansion of immunosuppressive cell populations to develop the tumor microenvironment or pre-metastatic niche but also switch the phenotype and function of normal immune cells from a potentially tumor-reactive state to a tumor-promoting state. Immunosuppressive cells facilitate tumor immune escape by inhibiting antitumor immune responses and furthermore promote tumor metastasis by inducing immunosuppression, promoting tumor cell invasion and intravasation, establishing a pre-metastatic niche, facilitating epithelial-mesenchymal transition, and inducing angiogenesis at primary tumor or metastatic sites. Numerous translational studies indicate that it is possible to inhibit tumor immune escape and prevent tumor metastasis by blocking immunosuppressive cells and eliminating immunosuppressive mechanisms that are induced by either immunosuppressive cells or tumor cells. Furthermore, many clinical trials targeting immunosuppressive cells have also achieved good outcome. In this review, we focus on the underlying mechanisms of immunosuppressive cells in promoting tumor immune escape and metastasis, discuss our current understanding of the interactions between immunosuppressive cells and tumor cells in the tumor microenvironment, and suggest future research directions as well as potential clinical strategies in cancer immunotherapy.

Keywords: Cancer immunotherapy; Immune escape; Immunosuppressive cell; Metastasis; Tumor microenvironment.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers
  • Epithelial-Mesenchymal Transition / genetics
  • Epithelial-Mesenchymal Transition / immunology
  • Humans
  • Immune System / cytology*
  • Immune System / immunology*
  • Immune System / metabolism
  • Immunologic Surveillance
  • Immunomodulation
  • Immunotherapy
  • Molecular Targeted Therapy
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Neoplasms / etiology*
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Neoplasms / therapy
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / immunology
  • Neovascularization, Pathologic / metabolism
  • Phenotype
  • Tumor Escape / immunology*
  • Tumor Microenvironment / immunology*


  • Biomarkers