NK cells and exercise: implications for cancer immunotherapy and survivorship

Discov Med. 2015 Jun;19(107):433-45.


Natural Killer (NK) cells are cytotoxic effectors of the innate immune system that are able to recognize and eradicate tumor cells without prior antigenic exposure. Tumor infiltration by NK-cells is associated with prolonged survival in cancer patients and high NK-cell cytotoxicity has been linked to decreased cancer risk. Allogeneic adoptive transfer of NK-cells from healthy donors to cancer patients has shown promise as a means of controlling or reversing the spread of multiple human malignancies including multiple myeloma and acute myeloid leukemia. However, multiple issues remain that undermine the efficacy of long-term cancer treatment using adoptive transfer of NK-cells including loss of activating receptors and cytotoxic potential in transferred NK-cells. Moreover, chronic exercise has been linked to improved NK-cell cytotoxicity, prognosis, and survival in cancer patients, and cytomegalovirus (CMV) reactivation is associated with enhanced NK-cell function after hematopoietic stem cell transplantation and decreased relapse risk in AML patients. In this work, we explore the potential of exercise- and CMV-driven alterations in NK-cell phenotype and function to increase the efficacy of NK-cells for cancer immunotherapy and prolong survival in cancer patients. We conclude that acute exercise and CMV are both capable of enhancing NK-cell cytotoxicity through distinct mechanisms; however, these effects are not additive as CMV infection is associated with an impaired acute exercise response. Thus, we suggest that either acute exercise or in vitro expansion of NKG2C+/NKG2A- NK-cells (as seen in those with CMV) could serve as a simple strategy for enhancing the anti-tumor cytotoxicity of NK-cells for immunotherapy, and that exercise training could be used to improve survivorship in cancer patients being treated with either HSCT or NK-cell infusions.

Publication types

  • Review

MeSH terms

  • Disease-Free Survival
  • Exercise*
  • Humans
  • Immunity, Cellular*
  • Immunotherapy*
  • Killer Cells, Natural / immunology*
  • Killer Cells, Natural / pathology
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myeloid, Acute / therapy*
  • Multiple Myeloma / immunology
  • Multiple Myeloma / pathology
  • Multiple Myeloma / therapy*
  • Survival Rate