On‐Chip Biogenesis of Circulating NK Cell‐Derived Exosomes in Non‐Small Cell Lung Cancer Exhibits Antitumoral Activity
Abstract As the recognition between natural killer (NK) cells and cancer cells does not require antigen presentation, NK cells are being actively studied for use in adoptive cell therapies in the rapidly evolving armamentarium of cancer immunotherapy. In addition to utilizing NK cells, recent studie...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-03-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202003747 |
| _version_ | 1818443523833200640 |
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| author | Yoon‐Tae Kang Zeqi Niu Thomas Hadlock Emma Purcell Ting‐Wen Lo Mina Zeinali Sarah Owen Venkateshwar G. Keshamouni Rishindra Reddy Nithya Ramnath Sunitha Nagrath |
| author_facet | Yoon‐Tae Kang Zeqi Niu Thomas Hadlock Emma Purcell Ting‐Wen Lo Mina Zeinali Sarah Owen Venkateshwar G. Keshamouni Rishindra Reddy Nithya Ramnath Sunitha Nagrath |
| author_sort | Yoon‐Tae Kang |
| collection | DOAJ |
| description | Abstract As the recognition between natural killer (NK) cells and cancer cells does not require antigen presentation, NK cells are being actively studied for use in adoptive cell therapies in the rapidly evolving armamentarium of cancer immunotherapy. In addition to utilizing NK cells, recent studies have shown that exosomes derived from NK cells also exhibit antitumor properties. Furthermore, these NK cell‐derived exosomes exhibit higher stability, greater modification potentials and less immunogenicity compared to NK cells. Therefore, technologies that allow highly sensitive and specific isolation of NK cells and NK cell‐derived exosomes can enable personalized NK‐mediated cancer therapeutics in the future. Here, a novel microfluidic system to collect patient‐specific NK cells and on‐chip biogenesis of NK‐exosomes is proposed. In a small cohort of non‐small cell lung cancer (NSCLC) patients, both NK cells and circulating tumor cells (CTCs) were isolated, and it is found NSCLC patients have high numbers of NK and NK‐exosomes compared with healthy donors, and these concentrations show a trend of positive and negative correlations with bloodborne CTC numbers, respectively. It is further demonstrated that the NK‐exosomes harvested from NK‐graphene oxide chip exhibit cytotoxic effect on CTCs. This versatile system is expected to be used for patient‐specific NK‐based immunotherapies along with CTCs for potential prognostic/diagnostic applications. |
| first_indexed | 2024-12-14T19:01:24Z |
| format | Article |
| id | doaj.art-1fe86000dcdb48de8238d16d2b30f982 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-12-14T19:01:24Z |
| publishDate | 2021-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-1fe86000dcdb48de8238d16d2b30f9822022-12-21T22:50:57ZengWileyAdvanced Science2198-38442021-03-0186n/an/a10.1002/advs.202003747On‐Chip Biogenesis of Circulating NK Cell‐Derived Exosomes in Non‐Small Cell Lung Cancer Exhibits Antitumoral ActivityYoon‐Tae Kang0Zeqi Niu1Thomas Hadlock2Emma Purcell3Ting‐Wen Lo4Mina Zeinali5Sarah Owen6Venkateshwar G. Keshamouni7Rishindra Reddy8Nithya Ramnath9Sunitha Nagrath10Department of Chemical Engineering Biointerfaces Institute University of Michigan Ann Arbor MI 48109 USADepartment of Chemical Engineering Biointerfaces Institute University of Michigan Ann Arbor MI 48109 USADepartment of Chemical Engineering Biointerfaces Institute University of Michigan Ann Arbor MI 48109 USADepartment of Chemical Engineering Biointerfaces Institute University of Michigan Ann Arbor MI 48109 USADepartment of Chemical Engineering Biointerfaces Institute University of Michigan Ann Arbor MI 48109 USADepartment of Chemical Engineering Biointerfaces Institute University of Michigan Ann Arbor MI 48109 USADepartment of Chemical Engineering Biointerfaces Institute University of Michigan Ann Arbor MI 48109 USAMichigan Medicine Pulmonary and Critical Care Division University of Michigan Ann Arbor MI 48109 USAMichigan Medicine Thoracic Surgery Clinic Taubman Center 1500E Medical Center Dr. SPC 5344 Ann Arbor MI 48109 USADepartment of Internal Medicine University of Michigan Ann Arbor MI 48109 USADepartment of Chemical Engineering Biointerfaces Institute University of Michigan Ann Arbor MI 48109 USAAbstract As the recognition between natural killer (NK) cells and cancer cells does not require antigen presentation, NK cells are being actively studied for use in adoptive cell therapies in the rapidly evolving armamentarium of cancer immunotherapy. In addition to utilizing NK cells, recent studies have shown that exosomes derived from NK cells also exhibit antitumor properties. Furthermore, these NK cell‐derived exosomes exhibit higher stability, greater modification potentials and less immunogenicity compared to NK cells. Therefore, technologies that allow highly sensitive and specific isolation of NK cells and NK cell‐derived exosomes can enable personalized NK‐mediated cancer therapeutics in the future. Here, a novel microfluidic system to collect patient‐specific NK cells and on‐chip biogenesis of NK‐exosomes is proposed. In a small cohort of non‐small cell lung cancer (NSCLC) patients, both NK cells and circulating tumor cells (CTCs) were isolated, and it is found NSCLC patients have high numbers of NK and NK‐exosomes compared with healthy donors, and these concentrations show a trend of positive and negative correlations with bloodborne CTC numbers, respectively. It is further demonstrated that the NK‐exosomes harvested from NK‐graphene oxide chip exhibit cytotoxic effect on CTCs. This versatile system is expected to be used for patient‐specific NK‐based immunotherapies along with CTCs for potential prognostic/diagnostic applications.https://doi.org/10.1002/advs.202003747cancer immunotherapycirculating tumor cellsexosome biogenesismicrofluidicsnatural killer cells |
| spellingShingle | Yoon‐Tae Kang Zeqi Niu Thomas Hadlock Emma Purcell Ting‐Wen Lo Mina Zeinali Sarah Owen Venkateshwar G. Keshamouni Rishindra Reddy Nithya Ramnath Sunitha Nagrath On‐Chip Biogenesis of Circulating NK Cell‐Derived Exosomes in Non‐Small Cell Lung Cancer Exhibits Antitumoral Activity Advanced Science cancer immunotherapy circulating tumor cells exosome biogenesis microfluidics natural killer cells |
| title | On‐Chip Biogenesis of Circulating NK Cell‐Derived Exosomes in Non‐Small Cell Lung Cancer Exhibits Antitumoral Activity |
| title_full | On‐Chip Biogenesis of Circulating NK Cell‐Derived Exosomes in Non‐Small Cell Lung Cancer Exhibits Antitumoral Activity |
| title_fullStr | On‐Chip Biogenesis of Circulating NK Cell‐Derived Exosomes in Non‐Small Cell Lung Cancer Exhibits Antitumoral Activity |
| title_full_unstemmed | On‐Chip Biogenesis of Circulating NK Cell‐Derived Exosomes in Non‐Small Cell Lung Cancer Exhibits Antitumoral Activity |
| title_short | On‐Chip Biogenesis of Circulating NK Cell‐Derived Exosomes in Non‐Small Cell Lung Cancer Exhibits Antitumoral Activity |
| title_sort | on chip biogenesis of circulating nk cell derived exosomes in non small cell lung cancer exhibits antitumoral activity |
| topic | cancer immunotherapy circulating tumor cells exosome biogenesis microfluidics natural killer cells |
| url | https://doi.org/10.1002/advs.202003747 |
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