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 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.

Engineered exosomes for co‐delivery of PGM5‐AS1 and oxaliplatin to reverse drug resistance in colon cancer

“…NR_015423 is termed PGM5‐AS1 in this study. The progression of esophageal squamous cell carcinoma and clear‐cell renal cell carcinoma has been reported to be inhibited by PGM5‐AS1 (Zhihua et al, 2019; Qian et al, 2019). Two recent reports, however, have recorded entirely different studies on the function of PGM5‐AS1 in CRC (Shen et al, 2021; B. Zhou et al, 2020), encouraging us to investigate the role and mechanism of PGM5‐AS1 in human CRC.…”

“…CRC, colorectal cancer; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; IgG, Immunoglobulin G; PGM5-AS1, PGM5 antisense RNA 1; mRNA, messenger RNA; RIP, RNA immunoprecipitation. *p < 0.05; **p < 0.01; ***p < 0.001 exosomes collected with an NK graphene oxide chip have tumorsuppressive effects(Kang et al, 2021). Exosomes have shown great promise in the early diagnosis and treatment of tumors, but how to improve the targeting and payload of exosomes is still an urgent problem(Xie et al, 2020).…”

Immune Cell-Derived Extracellular Vesicles – New Strategies in Cancer Immunotherapy

“…NK-derived EVs exhibited cytotoxic effects on circulating tumor cells (CTCs). This versatile system is expected to be used for patient-specific NK-based immunotherapies against CTCs for potential prognostic/diagnostic applications ( 57 ).…”

miRNAs in decidual NK cells: regulators worthy of attention during pregnancy

“…Of note, exosomes play crucial roles in the mediation of cell-to-cell communication at maternal-fetal interface [ 94 , 95 ], and it is worth exploring that whether above functional miRNAs can be transferred into dNK cells by ESCs/trophoblasts-derived exosomes in pregnancy related disorders, inducing dysfunctions of dNK cells and impairing immune system balance of pregnant women. In turn, NK cell-derived exosomes are identified to mediate cytotoxicity against tumor cells [ 96 , 97 ], and it is not known whether dNK cell can secrete miRNA-containing exosomes or micro-vesicles into maternal-fetal interface, which can affect systemic inflammation, decidualization and biological behavior of other decidual cells.…”

“…dNK cell, Decidual NK cell; pNK cell, Peripheral NK cell; RPL, Recurrent pregnancy loss; DEMs, Differentially expressed miRNAs balance of pregnant women. In turn, NK cell-derived exosomes are identified to mediate cytotoxicity against tumor cells [96,97], and it is known whether dNK cell can miRNA-containing exosomes or microvesicles into maternal-fetal interface, which can affect systemic inflammation, decidualization and biological behavior of other decidual cells.…”