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Exosomes derived from Vδ2-T cells control Epstein-Barr virus–associated tumors and induce T cell antitumor immunity.
- Source :
- Science Translational Medicine; 9/30/2020, Vol. 12 Issue 563, p1-16, 16p
- Publication Year :
- 2020
-
Abstract
- No holds barred for antitumor attack: Epstein-Barr virus (EBV) is a common pathogen that contributes to the development of several cancers, which can be difficult to treat. γδ-T cells have innate activity and have been proposed as a cancer immunotherapy, but they have been difficult to apply, particularly because they have to be individually prepared for each patient. To overcome the hurdles associated with whole γδ-T cell–based therapy, Wang et al. isolated exosomes from a subtype of activated γδ-T cells, which contained multiple immunostimulatory molecules and cell death–inducing ligands. These exosomes were effective against multiple mouse models of EBV-associated cancers and did not require customized preparation unlike cell-based therapies. Treatment of life-threatening Epstein-Barr virus (EBV)–associated tumors remains a great challenge, especially for patients with relapsed or refractory disease. Here, we found that exosomes derived from phosphoantigen-expanded Vδ2-T cells (Vδ2-T-Exos) contained death-inducing ligands (FasL and TRAIL), an activating receptor for natural killer (NK) cells (NKG2D), immunostimulatory ligands (CD80 and CD86), and antigen-presenting molecules (MHC class I and II). Vδ2-T-Exos targeted and efficiently killed EBV-associated tumor cells through FasL and TRAIL pathways and promoted EBV antigen–specific CD4 and CD8 T cell expansion. Administration of Vδ2-T-Exos effectively controlled EBV-associated tumors in Rag2<superscript>−/−</superscript>γc<superscript>−/−</superscript> and humanized mice. Because expanding Vδ2-T cells and preparing autologous Vδ2-T-Exos from cancer patients ex vivo in large scale is challenging, we explored the antitumor activity of allogeneic Vδ2-T-Exos in humanized mouse cancer models. Here, we found that allogeneic Vδ2-T-Exos had more effective antitumor activity than autologous Vδ2-T-Exos in humanized mice; the allogeneic Vδ2-T-Exos increased the infiltration of T cells into tumor tissues and induced more robust CD4 and CD8 T cell–mediated antitumor immunity. Compared with exosomes derived from NK cells (NK-Exos) with direct cytotoxic antitumor activity or dendritic cells (DC-Exos) that induced T cell antitumor responses, Vδ2-T-Exos directly killed tumor cells and induced T cell–mediated antitumor response, thus resulting in more effective control of EBV-associated tumors. This study provided proof of concept for the strategy of using Vδ2-T-Exos, especially allogeneic Vδ2-T-Exos, to treat EBV-associated tumors. [ABSTRACT FROM AUTHOR]
- Subjects :
- EXOSOMES
T cells
CYTOTOXIC T cells
KILLER cells
CELLS
CELLULAR immunity
TUMORS
Subjects
Details
- Language :
- English
- ISSN :
- 19466234
- Volume :
- 12
- Issue :
- 563
- Database :
- Complementary Index
- Journal :
- Science Translational Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 146148845
- Full Text :
- https://doi.org/10.1126/scitranslmed.aaz3426