From mice to humans: developments in cancer immunoediting
Michele W.L. Teng, … , Wolf-Herman Fridman, Mark J. Smyth
Michele W.L. Teng, … , Wolf-Herman Fridman, Mark J. Smyth
Published September 1, 2015; First published August 4, 2015
Citation Information: J Clin Invest. 2015;125(9):3338-3346. https://doi.org/10.1172/JCI80004.
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Category: Review Series

From mice to humans: developments in cancer immunoediting

Abstract

Cancer immunoediting explains the dual role by which the immune system can both suppress and/or promote tumor growth. Although cancer immunoediting was first demonstrated using mouse models of cancer, strong evidence that it occurs in human cancers is now accumulating. In particular, the importance of CD8+ T cells in cancer immunoediting has been shown, and more broadly in those tumors with an adaptive immune resistance phenotype. This Review describes the characteristics of the adaptive immune resistance tumor microenvironment and discusses data obtained in mouse and human settings. The role of other immune cells and factors influencing the effector function of tumor-specific CD8+ T cells is covered. We also discuss the temporal occurrence of cancer immunoediting in metastases and whether it differs from immunoediting in the primary tumor of origin.

Authors

Michele W.L. Teng, Jerome Galon, Wolf-Herman Fridman, Mark J. Smyth

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Figure 1

Major mechanisms of tumor escape and therapeutic options.

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Major mechanisms of tumor escape and therapeutic options. The mechanisms...
The mechanisms of tumor cell escape can be classified into three major categories: (A) reduced immune recognition and immune cell stimulation through downregulation or loss of strong tumor antigens and antigen-presenting machinery or lack of costimulatory molecules; (B) upregulation of resistance mechanisms against the cytotoxic effectors of immunity (e.g., STAT3) or increased expression of prosurvival or growth factor genes (e.g., Bcl-2, Her2/neu); and (C) establishment of an immunosuppressive tumor microenvironment via (a) production of cytokines (e.g., VEGF, TGF-β) and metabolic factors (e.g., adenosine, PGE2); (b) induction and/or recruitment of Tregs and MDSCs; or (c) induction of adaptive immune resistance through ligation of inhibitory receptors (e.g., CTLA-4, PD-1, Tim-3) on immune effector cells. Over the past two decades, strategies to target these pathways have been the subject of intense investigation, and some of these are listed in the figure. iNOS, inducible NOS.