In vivo Anti-Cancer Effects of Resveratrol Mediated by NK Cell Activation

J Innate Immun. 2021;13(2):94-106. doi: 10.1159/000510315. Epub 2020 Sep 16.


Natural killer (NK) cells are innate immune lymphocytes that play an important role in anti-viral and anti-tumour immune responses. Several cancer immunotherapy approaches targeting NK cells are currently in clinical or preclinical development. Here, we aimed to find food nutrients that activate NK cells and determine their usefulness as candidates for anti-cancer and anti-metastatic drugs. Resveratrol appeared to activate NK cells most effectively among the substances tested and synergistically increased IFN-γ secretion and NK cell cytotoxicity with interleukin-2 (IL-2). CD107a, NKp30, and NKG2D expression levels were upregulated on the surface of NK cells upon treatment with resveratrol in combination with IL-2 compared with treatment with IL-2 alone. Moreover, NK cell activity in human and mouse whole blood was enhanced upon treatment with resveratrol. Most importantly, administration of resveratrol effectively inhibited tumour growth and metastasis in mice. In conclusion, we suggest that resveratrol may represent a candidate anti-cancer drug that acts by activating NK cells in vivo.

Keywords: Immunotherapy; Interferon-gamma; Natural killer cell; Natural killer cytotoxicity; Resveratrol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Cytotoxicity, Immunologic
  • Female
  • Humans
  • Immunity, Innate
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism
  • Killer Cells, Natural / immunology*
  • Lymphocyte Activation
  • Lysosomal-Associated Membrane Protein 1 / metabolism
  • Melanoma, Experimental
  • Mice
  • NK Cell Lectin-Like Receptor Subfamily K
  • Natural Cytotoxicity Triggering Receptor 3 / metabolism
  • Neoplasm Metastasis
  • Neoplasms, Experimental / drug therapy*
  • Nutrients / metabolism*
  • Resveratrol / therapeutic use*
  • Tumor Burden / drug effects


  • Antineoplastic Agents
  • Interleukin-2
  • KLRK1 protein, human
  • Lysosomal-Associated Membrane Protein 1
  • NCR3 protein, human
  • NK Cell Lectin-Like Receptor Subfamily K
  • Natural Cytotoxicity Triggering Receptor 3
  • Interferon-gamma
  • Resveratrol