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B7-H4-mediated immunoresistance is supressed by PI3K/Akt/mTOR pathway inhibitors

  • Molecular Cell Biology
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Abstract

B7-H4 plays an important role in tumor immune evasion. In previous studies we have found that B7-H4 can translocate to the nucleus, and the exposure to PI3K inhibitor Ly294002 affects B7-H4 subcellular distribution. In this study we report the role of PI3K/Akt pathway in the B7-H4 subcellular distribution and the effect of PI3K/Akt inhibitors on B7-H4-mediated immunoresistance. The involvement of PI3K/Akt pathway in B7-H4 subcellular distribution was evident in experiments with wortmannin, while MDM2 inhibitor nutlin-3 and the mTOR inhibitor rapamycin were used to dissect the signaling downstream of Akt. Wortmannin and rapamycin demonstrated similar effects on B7-H4 subcellular distribution. Exposure to any of these inhibitors decreased levels of membrane B7-H4 while at the same time inducing its nuclear accumulation, while exposure to nutlin-3 had no effect on B7-H4 subcellular distribution. In the T cell proliferation assay, both wortmannin and rapamycin effectively inhibited B7-H4 WT/293 cells-mediated T cell proliferation while exerting no effect on Mock/293 cells. PI3K/Akt/mTOR plays a role in B7-H4 subcellular distribution, while MDM2 does not take part in it. Moreover, we show that wortmannin and rapamycin inhibit B7-H4-mediated tumor immunoresistance through regulating B7-H4 subcellular distribution. Taken together, these results suggest that PI3K/Akt/mTOR inhibitors might be used for adjuvant therapy aimed at inhibition of immune evasion.

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Authors and Affiliations

  1. Department of Biology Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, People’s Republic of China

    S. Zeng, H. Song, Y. Chen & L. Zhang

  2. Department of Immunology, School of Basic Medicine and Life Sciences, Medical College of Soochow University, Suzhou, 215123, People’s Republic of China

    W. Xie

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  1. S. Zeng
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  2. H. Song
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  3. Y. Chen
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  4. W. Xie
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  5. L. Zhang
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Correspondence to L. Zhang.

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Published in Russian in Molekulyarnaya Biologiya, 2016, Vol. 50, No. 6, pp. 1007–1013.

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Zeng, S., Song, H., Chen, Y. et al. B7-H4-mediated immunoresistance is supressed by PI3K/Akt/mTOR pathway inhibitors. Mol Biol 50, 887–894 (2016). https://doi.org/10.1134/S0026893316060248

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  • DOI: https://doi.org/10.1134/S0026893316060248

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