A analysis crew at LKS School of Drugs, The College of Hong Kong (HKUMed) found that exosomes derived from γδ-T cells (γδ-T-Exos) synergized with radiotherapy can management nasopharyngeal carcinoma (NPC) by overcoming the radioresistance of NPC most cancers stem cells (CSCs) and protect their tumor-killing and T cell-promoting actions within the immunosuppressive NPC microenvironment. This research offers a proof of idea for a novel and potent technique by combining γδ-T-Exos with radiotherapy within the management of NPC. The bottom-breaking findings have been printed within the main educational journal, Journal for Immunotherapy of Most cancers.
Nasopharyngeal carcinoma (NPC) is without doubt one of the most aggressive Epstein-Barr virus (EBV)-associated tumors, that are very prevalent in East Asia, together with Hong Kong. Radiotherapy is the first-line remedy for NPC, however its therapeutic efficacy is poor in some sufferers attributable to radioresistance. Adoptive T cell-based immunotherapy has additionally proven promise to manage NPC; nonetheless, its anti-tumor efficacy could also be attenuated by an immunosuppressive tumor microenvironment. Exosomes are endosome-originated small extracellular vesicles that mediate intercellular communication. In contrast with cell-based remedy, cell-free exosomes have benefits with larger security, simpler storage and decrease prices. In a earlier research, researchers have demonstrated that γδ-T-Exos may successfully management the development of EBV-associated tumors. Nonetheless, it stays unknown whether or not γδ-T-Exos have synergistic impact with radiotherapy and protect their anti-tumor actions towards NPC in an immunosuppressive tumour microenvironment.
Herein, the analysis crew discovered that γδ-T-Exos not solely successfully interacted with NPC cells and induced tumor cell loss of life in vitro, which was primarily mediated by Fas/Fas ligand (FasL) and loss of life receptor 5 (DR5)/tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathways, but additionally managed NPC tumor development and extended tumor-bearing mice survival in vivo. Moreover, γδ-T-Exos selectively focused the radioresistant CD44+/excessiveCSCs and induced profound cell apoptosis. The mix of γδ-T-Exos with radiotherapy overcame the radioresistance of CD44+/excessiveNPC cells and considerably improved its therapeutic efficacy towards NPC in vitro and in vivo. As well as, γδ-T-Exos promoted T-cell migration into NPC tumors by upregulating CCR5 on T cells that have been chemoattracted by CCR5 ligands within the NPC tumor microenvironment. Though NPC tumor cells secreted considerable tumor development issue beta (TGF-β) to suppress T- cell responses, γδ-T-Exos preserved their direct anti-tumor actions and overcame the immunosuppressive NPC microenvironment to amplify T-cell anti-tumor immunity.
‘Our research first offers a powerful pre-clinical proof of idea utilizing a novel therapeutic technique by combining γδ-T-Exos with radiotherapy to deal with NPC. γδ-T-Exos can successfully work together with and kill each EBV optimistic and destructive NPC cells. Extra importantly, γδ-T-Exos can eradicate radioresistant NPC CSCs and protect their tumor-killing and T cell-promoting actions within the immunosuppressive NPC microenvironment. Subsequently, mixture of radiotherapy with γδ-T- Exos has nice potential within the remedy of NPC, which will likely be extremely helpful to the medical software of this method,’ mentioned Professor Tu Wenwei of the Division of Paediatrics and Adolescent Drugs, College of Scientific Drugs, HKUMed, who led the analysis.
Significance of the research
The findings of the research have important implications in most cancers immunotherapy. Firstly, γδ-T-Exos interacted with CD44+/excessiveNPC CSCs in excessive efficacy. Subsequently, γδ-T-Exos can complement radiotherapy and improve its therapeutic efficacy towards NPC. Secondly, γδ-T-Exos has benefits over different exosome-based therapies together with ionizing irradiation in NPC remedy (e.g. MSC-Exos) by preserving anti-tumor actions within the immunosuppressive NPC microenvironment and are simpler in preparation. Thirdly, the outcomes that γδ-T-Exos expanded pre-existing tumor-specific T cells within the immunosuppressive NPC microenvironment can tremendously improve the medical feasibility of γδ-T-Exos. Subsequently, it will be significant for the mix remedy to own immunostimulatory results to spice up anti-tumor immunity within the immunosuppressive NPC microenvironment.
Wang, X., et al. (2022) Exosomes derived from γδ-T cells synergize with radiotherapy and protect antitumor actions towards nasopharyngeal carcinoma in immunosuppressive microenvironment. Journal for Immunotherapy of Most cancers. doi.org/10.1136/jitc-2021-003832.