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Soluble and Exosome-Bound α-Galactosylceramide Mediate Preferential Proliferation of Educated NK Cells with Increased Anti-Tumor Capacity
| Content Provider | MDPI |
|---|---|
| Author | Tanja, Näslund Klas, Kärre Wagner, Arnika Gehrmann, Ulf Hiltbrunner, Stefanie Carannante, Valentina Luu, Thuy Brauner, Hanna Kadri, Nadir Gabrielsson, Susanne |
| Copyright Year | 2021 |
| Description | Natural killer (NK) cells can kill target cells via the recognition of stress molecules and down-regulation of major histocompatibility complex class I (MHC-I). Some NK cells are educated to recognize and kill cells that have lost their MHC-I expression, e.g., tumor or virus-infected cells. A desired property of cancer immunotherapy is, therefore, to activate educated NK cells during anti-tumor responses in vivo. We here analyze NK cell responses to α-galactosylceramide (αGC), a potent activator of invariant NKT (iNKT) cells, or to exosomes loaded with αGC. In mouse strains which express different MHC-I alleles using an extended NK cell flow cytometry panel, we show that αGC induces a biased NK cell proliferation of educated NK cells. Importantly, iNKT cell-induced activation of NK cells selectively increased in vivo missing self-responses, leading to more effective rejection of tumor cells. Exosomes from antigen-presenting cells are attractive anti-cancer therapy tools as they may induce both innate and adaptive immune responses, thereby addressing the hurdle of tumor heterogeneity. Adding αGC to antigen-loaded dendritic-cell-derived exosomes also led to an increase in missing self-responses in addition to boosted T and B cell responses. This study manifests αGC as an attractive adjuvant in cancer immunotherapy, as it increases the functional capacity of educated NK cells and enhances the innate, missing self-based antitumor response. |
| Starting Page | 298 |
| e-ISSN | 20726694 |
| DOI | 10.3390/cancers13020298 |
| Journal | Cancers |
| Issue Number | 2 |
| Volume Number | 13 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-01-15 |
| Access Restriction | Open |
| Subject Keyword | Cancers Oncology Extracellular Vesicles Exosomes Natural Killer (nk) Cells Innate Anti-tumor Response Missing-self Response Antitumor Immunity Nk Cell Education Mhc Class I |
| Content Type | Text |
| Resource Type | Article |
