Sufficiently activated mature natural killer cells derived from peripheral blood mononuclear cells substantially enhance antitumor activity
Abstract Background Peripheral blood‐derived natural killer (NK) cells spontaneously lyse tumor cells without prior sensitization. However, NK cells in peripheral blood (PBNK cells) are in a resting state and exhibit inhibitory phenotypes and impaired cytotoxicity. Thus, strengthening the cytotoxic...
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| Format: | Article |
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Wiley
2024-01-01
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| Series: | Immunity, Inflammation and Disease |
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| Online Access: | https://doi.org/10.1002/iid3.1143 |
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| author | Chuanling Liu Yingying Li Yanrong Li Meng Hu Haiyan Wang Shasha Lu Zhao Li Dilinuer Dilimulati Shunchang Jiao Shelian Lu Weihong Zhao |
| author_facet | Chuanling Liu Yingying Li Yanrong Li Meng Hu Haiyan Wang Shasha Lu Zhao Li Dilinuer Dilimulati Shunchang Jiao Shelian Lu Weihong Zhao |
| author_sort | Chuanling Liu |
| collection | DOAJ |
| description | Abstract Background Peripheral blood‐derived natural killer (NK) cells spontaneously lyse tumor cells without prior sensitization. However, NK cells in peripheral blood (PBNK cells) are in a resting state and exhibit inhibitory phenotypes and impaired cytotoxicity. Thus, strengthening the cytotoxic effector function of PBNK cells and improving NK cell expansion in vitro for a convenient allogeneic therapy are essential. Materials and Methods Pure cytokine activation and expansion of NK cells (super NK [SNK]) from peripheral blood mononuclear cells were studied. Markers of activated and inhibited NK cells and cytokine secretion by NK cells were examined using flow cytometry. NK cell antitumor activity in vitro was assessed using lactate dehydrogenase (LDH) cytotoxicity assay and an Incucyte real‐time imaging system. Additionally, the function of SNK cells against ascites caused by ovarian cancer in NOD‐Prkdc(em26Cd52)il2rg(em26Cd22)/Nju (NCG) mice was determined. In a further investigation of the differences between PBNK and SNK, the mRNA of both cells was sequenced and analyzed. Results Human peripheral blood mononuclear cells showed selective NK cell expansion upon cytokine activation and culture. Both SNK and PBNK cells expressed activation markers, but at different levels, and SNK cells secreted more cytokines related to cytotoxicity than PBNK cells did. Accordingly, SNK cells exhibited strong antitumor activity ex vivo and improved NCG mice survival after intraperitoneal ovarian cancer transplantation. Mechanistically, SNK cells expressed more genes associated with nucleotide metabolism, fatty acid, and ATP metabolism than PBNK cells. Conclusion SNK cells derived from peripheral blood mononuclear cells have sufficiently activated mature characteristics and high antitumor activity, rendering them a highly promising and essential therapeutic approach for cancer treatment. |
| format | Article |
| id | doaj-art-5ad9560eed704061b8c5cb1c3f2ea43e |
| institution | Kabale University |
| issn | 2050-4527 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Immunity, Inflammation and Disease |
| spelling | doaj-art-5ad9560eed704061b8c5cb1c3f2ea43e2025-08-20T03:24:11ZengWileyImmunity, Inflammation and Disease2050-45272024-01-01121n/an/a10.1002/iid3.1143Sufficiently activated mature natural killer cells derived from peripheral blood mononuclear cells substantially enhance antitumor activityChuanling Liu0Yingying Li1Yanrong Li2Meng Hu3Haiyan Wang4Shasha Lu5Zhao Li6Dilinuer Dilimulati7Shunchang Jiao8Shelian Lu9Weihong Zhao10Department of Oncology Chinese PLA General Hospital Beijing ChinaResearch and Development Department Beijing DCTY® Biotech Co., Ltd Beijing ChinaResearch and Development Department Beijing DCTY® Biotech Co., Ltd Beijing ChinaResearch and Development Department Beijing DCTY® Biotech Co., Ltd Beijing ChinaResearch and Development Department Beijing DCTY® Biotech Co., Ltd Beijing ChinaResearch and Development Department Beijing DCTY® Biotech Co., Ltd Beijing ChinaResearch and Development Department Beijing DCTY® Biotech Co., Ltd Beijing ChinaResearch and Development Department Beijing DCTY® Biotech Co., Ltd Beijing ChinaDepartment of Oncology Chinese PLA General Hospital Beijing ChinaResearch and Development Department Beijing DCTY® Biotech Co., Ltd Beijing ChinaDepartment of Oncology Chinese PLA General Hospital Beijing ChinaAbstract Background Peripheral blood‐derived natural killer (NK) cells spontaneously lyse tumor cells without prior sensitization. However, NK cells in peripheral blood (PBNK cells) are in a resting state and exhibit inhibitory phenotypes and impaired cytotoxicity. Thus, strengthening the cytotoxic effector function of PBNK cells and improving NK cell expansion in vitro for a convenient allogeneic therapy are essential. Materials and Methods Pure cytokine activation and expansion of NK cells (super NK [SNK]) from peripheral blood mononuclear cells were studied. Markers of activated and inhibited NK cells and cytokine secretion by NK cells were examined using flow cytometry. NK cell antitumor activity in vitro was assessed using lactate dehydrogenase (LDH) cytotoxicity assay and an Incucyte real‐time imaging system. Additionally, the function of SNK cells against ascites caused by ovarian cancer in NOD‐Prkdc(em26Cd52)il2rg(em26Cd22)/Nju (NCG) mice was determined. In a further investigation of the differences between PBNK and SNK, the mRNA of both cells was sequenced and analyzed. Results Human peripheral blood mononuclear cells showed selective NK cell expansion upon cytokine activation and culture. Both SNK and PBNK cells expressed activation markers, but at different levels, and SNK cells secreted more cytokines related to cytotoxicity than PBNK cells did. Accordingly, SNK cells exhibited strong antitumor activity ex vivo and improved NCG mice survival after intraperitoneal ovarian cancer transplantation. Mechanistically, SNK cells expressed more genes associated with nucleotide metabolism, fatty acid, and ATP metabolism than PBNK cells. Conclusion SNK cells derived from peripheral blood mononuclear cells have sufficiently activated mature characteristics and high antitumor activity, rendering them a highly promising and essential therapeutic approach for cancer treatment.https://doi.org/10.1002/iid3.1143ascitesnatural killer cellovarian cancerperipheral blood |
| spellingShingle | Chuanling Liu Yingying Li Yanrong Li Meng Hu Haiyan Wang Shasha Lu Zhao Li Dilinuer Dilimulati Shunchang Jiao Shelian Lu Weihong Zhao Sufficiently activated mature natural killer cells derived from peripheral blood mononuclear cells substantially enhance antitumor activity Immunity, Inflammation and Disease ascites natural killer cell ovarian cancer peripheral blood |
| title | Sufficiently activated mature natural killer cells derived from peripheral blood mononuclear cells substantially enhance antitumor activity |
| title_full | Sufficiently activated mature natural killer cells derived from peripheral blood mononuclear cells substantially enhance antitumor activity |
| title_fullStr | Sufficiently activated mature natural killer cells derived from peripheral blood mononuclear cells substantially enhance antitumor activity |
| title_full_unstemmed | Sufficiently activated mature natural killer cells derived from peripheral blood mononuclear cells substantially enhance antitumor activity |
| title_short | Sufficiently activated mature natural killer cells derived from peripheral blood mononuclear cells substantially enhance antitumor activity |
| title_sort | sufficiently activated mature natural killer cells derived from peripheral blood mononuclear cells substantially enhance antitumor activity |
| topic | ascites natural killer cell ovarian cancer peripheral blood |
| url | https://doi.org/10.1002/iid3.1143 |
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