On-Chip Biogenesis of Circulating NK Cell-Derived Exosomes in Non-Small Cell Lung Cancer Exhibits Antitumoral Activity.

cancer immunotherapy circulating tumor cells exosome biogenesis microfluidics natural killer cells

Journal

Advanced science (Weinheim, Baden-Wurttemberg, Germany)
ISSN: 2198-3844
Titre abrégé: Adv Sci (Weinh)
Pays: Germany
ID NLM: 101664569

Informations de publication

Date de publication:
Mar 2021
Historique:
received: 30 09 2020
revised: 14 11 2020
entrez: 22 3 2021
pubmed: 23 3 2021
medline: 23 3 2021
Statut: epublish

Résumé

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.

Identifiants

pubmed: 33747745
doi: 10.1002/advs.202003747
pii: ADVS2314
pmc: PMC7967048
doi:

Types de publication

Journal Article

Langues

eng

Pagination

2003747

Informations de copyright

© 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH.

Déclaration de conflit d'intérêts

S.N. is one of the named inventors on a patent for Microfluidic Labyrinth Technology granted to the University of Michigan. S.N. is also the co‐founder of Labyrinth Biotech Inc. The funders and the company had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

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Auteurs

Yoon-Tae Kang (YT)

Department of Chemical Engineering Biointerfaces Institute University of Michigan Ann Arbor MI 48109 USA.

Zeqi Niu (Z)

Department of Chemical Engineering Biointerfaces Institute University of Michigan Ann Arbor MI 48109 USA.

Thomas Hadlock (T)

Department of Chemical Engineering Biointerfaces Institute University of Michigan Ann Arbor MI 48109 USA.

Emma Purcell (E)

Department of Chemical Engineering Biointerfaces Institute University of Michigan Ann Arbor MI 48109 USA.

Ting-Wen Lo (TW)

Department of Chemical Engineering Biointerfaces Institute University of Michigan Ann Arbor MI 48109 USA.

Mina Zeinali (M)

Department of Chemical Engineering Biointerfaces Institute University of Michigan Ann Arbor MI 48109 USA.

Sarah Owen (S)

Department of Chemical Engineering Biointerfaces Institute University of Michigan Ann Arbor MI 48109 USA.

Venkateshwar G Keshamouni (VG)

Michigan Medicine Pulmonary and Critical Care Division University of Michigan Ann Arbor MI 48109 USA.

Rishindra Reddy (R)

Michigan Medicine Thoracic Surgery Clinic Taubman Center 1500E Medical Center Dr. SPC 5344 Ann Arbor MI 48109 USA.

Nithya Ramnath (N)

Department of Internal Medicine University of Michigan Ann Arbor MI 48109 USA.

Sunitha Nagrath (S)

Department of Chemical Engineering Biointerfaces Institute University of Michigan Ann Arbor MI 48109 USA.
Rogel Cancer Center University of Michigan 1500 East Medical Center Drive Ann Arbor MI 48109 USA.

Classifications MeSH