Natural Killer Cells (NK cells) Based Immunotherapy in Treatment of Cancer: Current Progression and Remained Challenges

Shuoming Shang


Natural Killer Cells (NK cells) based immunotherapy involving a variety of immune checkpoint inhibitors (ICIs) is becoming increasingly common and has achieved considerable success. However, at the same time, it also faces some huge burning problems. Cancer immunotherapy with NK cells enables the precise elimination of cancer cells. Besides, NK cells can be massively expanded in vitro and do not lead to graft-versus-host-disease (GVHD). Furthermore, ICIs are capable to augment the tumoricidal capacity of NK cells. These characteristics make NK cells dominated immunotherapy a key player in cancer treatment.


Natural Killer Cell (NK Cell); Immune Checkpoint Inhibitors (ICIs)

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Shimasaki, N., Jain, A., & Campana, D. (2020). NK cells for cancer immunotherapy. Nature Reviews. Drug Discovery, 19(3), 200-218.

Hsu, J., Hodgins, J. J., Marathe, M., Nicolai, C. J., Bourgeois-Daigneault, M., Trevino, T. N., Azimi, C. S., Scheer, A. K., Randolph, H. E., Thompson, T. W., Zhang, L.,Iannello, A., Mathur, N., Jardine, K. E., Kirn, G. A., Bell, J. C., McBurney, M. W., Raulet, D. H., & Ardolino, M. (2018). Contribution of NK cells to immunotherapy mediated by PD-1/PD-L1 blockade. The Journal of Clinical Investigation, 128(10), 4654-4668.

Hanahan, D., & Weinberg, R. (2011). Hallmarks of cancer: The next generation. Cell (Cambridge), 144(5), 646-674.

Quezada, S. A., Peggs, K. S., Simpson, T. R., & Allison, J. P. (2011). Shifting the equilibrium in cancer immunoediting: From tumor tolerance to eradication. Immunological Reviews, 241(1), 104-118.

Korangy, F., Höchst, B., Manns, M. P., & Greten, T. F. (2010). Immune responses in hepatocellular carcinoma. Digestive Diseases (Basel), 28(1), 150-154.

Schreiber, R. D., Old, L. J., & Smyth, M. J. (2011). Cancer immunoediting: Integrating immunity's roles in cancer suppression and promotion. Science (American Association for the Advancement of Science), 331(6024), 1565-1570.

Suen, W. C., Lee, W. Y., Leung, K., Pan, X., & Li, G. (2018). Natural killer cell-based cancer immunotherapy: A review on 10 years completed clinical trials. Cancer Investigation, 36(8), 431-457.

André, P., Denis, C., Soulas, C., Bourbon-Caillet, C., Lopez, J., Arnoux, T., Bléry, M., Bonnafous, C., Gauthier, L., Morel, A., Rossi, B., Remark, R., Breso, V., Bonnet, E., Habif, G., Guia, S., Lalanne, A. I., Hoffmann, C., Lantz, O., . . . Vivier, E. (2018). Anti-NKG2A mAb is a checkpoint inhibitor that promotes anti-tumor immunity by unleashing both T and NK cells. Cell (Cambridge), 175(7), 1731-1743.e13.

Kamiya, T., Seow, S. V., Wong, D., Robinson, M., & Campana, D. (2019). Blocking expression of inhibitory receptor NKG2A overcomes tumor resistance to NK cells. The Journal of Clinical Investigation, 129(5), 2094-2106.

Böttcher, J. P., Bonavita, E., Chakravarty, P., Blees, H., Cabeza-Cabrerizo, M., Sammicheli, S., Rogers, N. C., Sahai, E., Zelenay, S., & Reis e Sousa, C. (2018). NK cells stimulate recruitment of cDC1 into the tumor microenvironment promoting cancer immune control. Cell (Cambridge), 172(5), 1022-1037.e14.

Cancel, J., Crozat, K., Dalod, M., & Mattiuz, R. (2019). Are conventional type 1 dendritic cells critical for protective antitumor immunity and how? Frontiers in Immunology, 10, 9-9.

Ames, E., Canter, R. J., Grossenbacher, S. K., Mac, S., Smith, R. C., Monjazeb, A. M., Chen, M., & Murphy, W. J. (2015). Enhanced targeting of stem-like solid tumor cells with radiation and natural killer cells. Oncoimmunology, 4(9), e1036212-e1036212.

Lugade, A. A., Moran, J. P., Gerber, S. A., Rose, R. C., Frelinger, J. G., & Lord, E. M. (2005). Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor. The Journal of Immunology (1950), 174(12), 7516-7523.

Kim, K. W., Jeong, J., Lee, K., Uong, T. N. T., Rhee, J. H., Ahn, S., Kim, S., Cho, D., Quang Nguyen, H. P., Pham, C. T., & Yoon, M. S. (2020). Combined NK cell therapy and radiation therapy exhibit long-term therapeutic and antimetastatic effects in a human triple negative breast cancer model. International Journal of Radiation Oncology, Biology, Physics, 108(1), 115-125.

Kokowski, K., Stangl, S., Seier, S., Hildebrandt, M., Vaupel, P., & Multhoff, G. (2019). Radiochemotherapy combined with NK cell transfer followed by second-line PD-1 inhibition in a patient with NSCLC stage IIIb inducing long-term tumor control: A case study. Strahlentherapie Und Onkologie, 195(4), 352-361.

Seo, H., Kim, B.-S., Bae, E.-A., Min, B. S., Han, Y. D., Shin, S. J., & Kang, C.-Y. (2018). IL21 Therapy Combined with PD-1 and Tim-3 Blockade Provides Enhanced NK Cell Antitumor Activity against MHC Class I–Deficient Tumors. Cancer Immunology Research, 6(6), 685.

DOI: http://dx.doi.org/10.18282/pmr.v10i2.2622


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