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Tumor PD-L1 Induction by Resveratrol/Piceatannol May Function as a Search, Enhance, and Engage (“SEE”) Signal to Facilitate the Elimination of “Cold, Non-Responsive” Low PD-L1-Expressing Tumors by PD-L1 Blockade

Department of Biochemistry and Molecular Biology, New York Medical College, Room 147, Valhalla, NY 10595, USA
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Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(23), 5969; https://doi.org/10.3390/ijms20235969
Received: 4 November 2019 / Revised: 22 November 2019 / Accepted: 25 November 2019 / Published: 27 November 2019
Programmed cell death ligand 1 (PD-L1) is an immune regulatory protein that facilitates tumor escape from host immune surveillance. In the clinic, tumors with high level of PD-L1 have been used to identify patients who might respond favorably to treatment by anti-PD-L1 antibodies (PD-L1 blockade, PLB). Typically, a progression-free response of 9–20% to PLB has been observed, the basis for the low success rate is largely unknown. Recently, we show upregulation of PD-L1 in cancer cells by ≥IC50 supra-pharmacological dose of grape polyphenol resveratrol and piceatannol, alone and combined. Herein, we summarize recent published studies on the regulation of tumor PD-L1 by flavonoids and grape polyphenols. We hypothesize that the induced tumor PD-L1 by resveratrol and/or piceatannol may serve as a Search, Enhance, and Engage (“SEE”) signal to sensitize and augment the recognition and detection of low PD-L1-expressing “cold, non-responsive” tumors. The “SEE” strategy enhances the “visibility” of previously unidentified tumor cells for targeting and eventual eradication by the host antitumor activity. This strategy expands the selection criteria for patients with improved sensitivity and potential responsiveness when used in combination with PLB. The modulation of tumor PD-L1 by flavonoids or polyphenols is proposed to improve the response to PLB in low PD-L1 tumors. View Full-Text
Keywords: dietary polyphenols; resveratrol; piceatannol; PD-L1 dietary polyphenols; resveratrol; piceatannol; PD-L1
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MDPI and ACS Style

Hsieh, T.-C.; Wu, J.M. Tumor PD-L1 Induction by Resveratrol/Piceatannol May Function as a Search, Enhance, and Engage (“SEE”) Signal to Facilitate the Elimination of “Cold, Non-Responsive” Low PD-L1-Expressing Tumors by PD-L1 Blockade. Int. J. Mol. Sci. 2019, 20, 5969. https://doi.org/10.3390/ijms20235969

AMA Style

Hsieh T-C, Wu JM. Tumor PD-L1 Induction by Resveratrol/Piceatannol May Function as a Search, Enhance, and Engage (“SEE”) Signal to Facilitate the Elimination of “Cold, Non-Responsive” Low PD-L1-Expressing Tumors by PD-L1 Blockade. International Journal of Molecular Sciences. 2019; 20(23):5969. https://doi.org/10.3390/ijms20235969

Chicago/Turabian Style

Hsieh, Tze-Chen, and Joseph M. Wu 2019. "Tumor PD-L1 Induction by Resveratrol/Piceatannol May Function as a Search, Enhance, and Engage (“SEE”) Signal to Facilitate the Elimination of “Cold, Non-Responsive” Low PD-L1-Expressing Tumors by PD-L1 Blockade" International Journal of Molecular Sciences 20, no. 23: 5969. https://doi.org/10.3390/ijms20235969

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