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PTEN at the interface of immune tolerance and tumor suppression

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  • Published:
Frontiers in Biology

Abstract

Background

PTEN is well known to function as a tumor suppressor that antagonizes oncogenic signaling and maintains genomic stability. The PTEN gene is frequently deleted or mutated in human cancers and the wide cancer spectrum associated with PTEN deficiency has been recapitulated in a variety of mouse models of Pten deletion or mutation. Pten mutations are highly penetrant in causing various types of spontaneous tumors that often exhibit resistance to anticancer therapies including immunotherapy. Recent studies demonstrate that PTEN also regulates immune functionality.

Objective

To understand the multifaceted functions of PTEN as both a tumor suppressor and an immune regulator.

Methods

This review will summarize the emerging knowledge of PTEN function in cancer immunoediting. In addition, the mechanisms underlying functional integration of various PTEN pathways in regulating cancer evolution and tumor immunity will be highlighted.

Results

Recent preclinical and clinical studies revealed the essential role of PTEN in maintaining immune homeostasis, which significantly expands the repertoire of PTEN functions. Mechanistically, aberrant PTEN signaling alters the interplay between the immune system and tumors, leading to immunosuppression and tumor escape.

Conclusion

Rational design of personalized anti-cancer treatment requires mechanistic understanding of diverse PTEN signaling pathways in modulation of the crosstalk between tumor and immune cells.

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Acknowledgements

Work in the authors’ laboratory is supported by NIH grant R01GM100478 and the Irma T. Hirschl/Monique Weill-Caulier Trust.

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Authors and Affiliations

  1. Department of Radiation Oncology, Weill Cornell Medicine, Cornell University, New York, NY, 10065, USA

    Andrew Brandmaier, Sheng-Qi Hou, Sandra Demaria, Silvia C. Formenti & Wen H. Shen

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  1. Andrew Brandmaier
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  2. Sheng-Qi Hou
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  3. Sandra Demaria
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  4. Silvia C. Formenti
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  5. Wen H. Shen
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Correspondence to Wen H. Shen.

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Brandmaier, A., Hou, SQ., Demaria, S. et al. PTEN at the interface of immune tolerance and tumor suppression. Front. Biol. 12, 163–174 (2017). https://doi.org/10.1007/s11515-017-1443-5

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  • DOI: https://doi.org/10.1007/s11515-017-1443-5

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