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Antitumor effects of NK cells expanded by activation pre‑processing of autologous feeder cells before irradiation in colorectal cancer

  • Authors:
    • Eun-Kyoung Koh
    • Hong-Rae Lee
    • Woo-Chang Son
    • Ga-Young Park
    • Jaeho Bae
    • You-Soo Park
  • View Affiliations / Copyright

    Affiliations: Department of Research Center, Dongnam Institute of Radiological & Medical Sciences, Gijang‑gun, Busan 46033, Republic of Korea, Department of Biochemistry, Pusan National University School of Medicine, Yangsan, Gyeongsangnam‑do 50612, Republic of Korea
    Copyright: © Koh et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 232
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    Published online on: April 18, 2023
       https://doi.org/10.3892/ol.2023.13818
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Abstract

Natural killer (NK) cells play a crucial role in early immune defenses against transformed cells and are used in the therapeutic management of cancer. However, it is difficult to sufficiently obtain high purity activated NK cells for clinical application. The function of NK cells is dependent on the balance of activating and inhibitory signals. Strong and diverse stimuli are required to increase the function of NK cells. Radiotherapy modulates the expression of various immunomodulatory molecules that recruit and activate NK cells. NK cell‑mediated antibody‑dependent cellular cytotoxicity is one of the most potent cytotoxic effects of NK cells against target cancer cells. To generate activated and irradiated autologous peripheral blood mononuclear cells (PBMCs), cytokine and monoclonal antibody stimulation followed by ionizing radiation was performed in the present study. The expanded NK cells were cultured for 21 days using activated/irradiated autologous PBMCs. Colorectal cancer cells (SW480 and HT‑29) were used to analyze the expression of NK group 2D ligands and EGFR by radiation. The cytotoxicity of radiation plus NK cell‑based targeted therapy against colorectal cancer cell lines was analyzed using flow cytometry. Activated and irradiated PBMCs exhibited significantly increased expression of various activating ligands that stimulated NK cells. In total, >10,000‑fold high‑purity activated NK cells were obtained, with negligible T‑cell contamination. To confirm the antitumor activity of the NK cells expanded by this method, the expanded NK cells were treated with cetuximab, radiotherapy, or a combination of cetuximab and radiotherapy in the presence of human colorectal cancer cells. Expanded NK cells were effective at targeting human colorectal cancer cells, particularly when combined with cetuximab and radiotherapy. Thus, in the present study, a novel method for high‑purity activated NK cell expansion was developed using activated and irradiated PBMCs. In addition, combined radiotherapy and antibody‑based immunotherapy with expanded NK cells may be an effective strategy to enhance the efficiency of treatment against colorectal cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Koh E, Lee H, Son W, Park G, Bae J and Park Y: Antitumor effects of NK cells expanded by activation pre‑processing of autologous feeder cells before irradiation in colorectal cancer. Oncol Lett 25: 232, 2023.
APA
Koh, E., Lee, H., Son, W., Park, G., Bae, J., & Park, Y. (2023). Antitumor effects of NK cells expanded by activation pre‑processing of autologous feeder cells before irradiation in colorectal cancer. Oncology Letters, 25, 232. https://doi.org/10.3892/ol.2023.13818
MLA
Koh, E., Lee, H., Son, W., Park, G., Bae, J., Park, Y."Antitumor effects of NK cells expanded by activation pre‑processing of autologous feeder cells before irradiation in colorectal cancer". Oncology Letters 25.6 (2023): 232.
Chicago
Koh, E., Lee, H., Son, W., Park, G., Bae, J., Park, Y."Antitumor effects of NK cells expanded by activation pre‑processing of autologous feeder cells before irradiation in colorectal cancer". Oncology Letters 25, no. 6 (2023): 232. https://doi.org/10.3892/ol.2023.13818
Copy and paste a formatted citation
x
Spandidos Publications style
Koh E, Lee H, Son W, Park G, Bae J and Park Y: Antitumor effects of NK cells expanded by activation pre‑processing of autologous feeder cells before irradiation in colorectal cancer. Oncol Lett 25: 232, 2023.
APA
Koh, E., Lee, H., Son, W., Park, G., Bae, J., & Park, Y. (2023). Antitumor effects of NK cells expanded by activation pre‑processing of autologous feeder cells before irradiation in colorectal cancer. Oncology Letters, 25, 232. https://doi.org/10.3892/ol.2023.13818
MLA
Koh, E., Lee, H., Son, W., Park, G., Bae, J., Park, Y."Antitumor effects of NK cells expanded by activation pre‑processing of autologous feeder cells before irradiation in colorectal cancer". Oncology Letters 25.6 (2023): 232.
Chicago
Koh, E., Lee, H., Son, W., Park, G., Bae, J., Park, Y."Antitumor effects of NK cells expanded by activation pre‑processing of autologous feeder cells before irradiation in colorectal cancer". Oncology Letters 25, no. 6 (2023): 232. https://doi.org/10.3892/ol.2023.13818
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