Natural killer (NK) cells have the innate ability to kill cancer cells, however, tumor cells may acquire the capability of evading the immune response, thereby leading to malignancies. Restoring or potentiation of this natural antitumor activity of NK cells has become a relevant therapeutic approach in cancer and, particularly, in hematological cancers. The use of tumor-specific antibodies that promote antibody-dependent cell-mediated cytotoxicity (ADCC) through the ligation of CD16 receptor on NK cells has become standard for many hematologic malignancies. Hematopoietic stem cell transplantation is another key therapeutic strategy that harnesses the alloreactivity of NK cells against cancer cells. This strategy may be refined by adoptive transfer of NK cells that may be previously expanded, activated, or redirected (chimeric antigen receptor (CAR)-NK cells) against cancer cells. The antitumor activity of NK cells can also be boosted by cytokines or immunostimulatory drugs such as lenalidomide or pomalidomide. Finally, targeting immunosubversive mechanisms developed by hematological cancers and, in particular, using antibodies that block NK cell inhibitory receptors and checkpoint proteins are novel promising therapeutic approaches in these malignant diseases.
Keywords: CAR-NK; NK cells; cancer; checkpoint; hematopoietic stem cell transplantation; immunotherapy.
Conflict of interest statement
The authors declare no conflicts of interest.
NK Cell-Based Immunotherapy for Hematological MalignanciesS Sivori et al. J Clin Med 8 (10). PMID 31623224. - ReviewNatural killer (NK) lymphocytes are an integral component of the innate immune system and represent important effector cells in cancer immunotherapy, particularly in the …
NK Cell-Based Immunotherapy in Cancer MetastasisS Lorenzo-Herrero et al. Cancers (Basel) 11 (1). PMID 30597841. - ReviewMetastasis represents the leading cause of cancer-related death mainly owing to the limited efficacy of current anticancer therapies on advanced malignancies. Although im …
Chimeric Antigen Receptor (CAR)-transduced Natural Killer Cells in Tumor ImmunotherapyY Hu et al. Acta Pharmacol Sin 39 (2), 167-176. PMID 28880014. - ReviewNatural killer (NK) cells are potential effector cells in cell-based cancer immunotherapy, particularly in the control of hematological malignancies. The chimeric antigen …
Tumor Immunotherapy: New Aspects of Natural Killer CellsY Li et al. Chin J Cancer Res 30 (2), 173-196. PMID 29861604.A group of impressive immunotherapies for cancer treatment, including immune checkpoint-blocking antibodies, gene therapy and immune cell adoptive cellular immunotherapy, …
Chimeric Antigen Receptor Expressing Natural Killer Cells for the Immunotherapy of CancerRS Mehta et al. Front Immunol 9, 283. PMID 29497427. - ReviewAdoptive cell therapy has emerged as a powerful treatment for advanced cancers resistant to conventional agents. Most notable are the remarkable responses seen in patient …