Antigen-loaded exosomes alone induce Th1-type memory through a B cell–dependent mechanism

Qazi, Khaleda Rahman; Gehrmann, Ulf; Jordö, Emilie Domange; Karlsson, Mikael C. I.; Gabrielsson, Susanne

doi:10.1182/blood-2008-04-153536

Cited by 204 publications

(253 citation statements)

References 43 publications

Supporting

Mentioning

239

Contrasting

Order By: Relevance

“…In phase I clinical trials, dexosomes were loaded with tumor-specific MHC class I and II peptides, both directly and indirectly (12,13). However, we showed that protein-loaded dexosomes were superior to peptide-loaded ones in activating CD4 + T cells in vivo, an effect due to B cell-mediated CD4 + T cell activation (15 In this study, we show that dexosomes induce CD8 + T cell responses in a CD4 + T cell-dependent manner. Importantly, B cells were also shown to be necessary for the optimal activation of CD8 + T cells.…”

mentioning

confidence: 56%

Dendritic Cell–Derived Exosomes Need To Activate Both T and B Cells To Induce Antitumor Immunity

Näslund

Gehrmann

Qazi

et al. 2013

The Journal of Immunology

Self Cite

167

156

View full text Add to dashboard Cite

Exosomes are secreted membrane nanovesicles of endosomal origin and are considered potential cancer vaccine vectors. Phase I clinical trials have been successfully conducted with tumor peptide–loaded exosomes derived from dendritic cells (dexosomes), and a phase II clinical trial is ongoing. However, much is still unknown regarding the in vivo role of dexosomes and whether their immunogenicity can be enhanced. We previously reported that dexosomes induce CD4+ T cell responses in a B cell–dependent manner, suggesting that immunization with dexosomes carrying only T cell peptides induce suboptimal immune responses. In this study, we show that CD8+ T cell responses were induced in vivo when mice were immunized with protein-loaded, but not peptide-loaded, dexosomes. We also show that the cytotoxic T cell response was totally dependent on CD4+ T cells and, interestingly, also on B cells. Mice deficient in complement activation and Ag shuttling by B cells have lower responses to protein-loaded dexosomes, showing involvement of these B cell–mediated mechanisms. Finally, protein-loaded dexosomes were superior in protecting against tumor growth. In conclusion, proper activation of CD4+ T and B cells needs to be considered when designing cancer vaccines to ensure full potential of the treatment.

show abstract

mentioning

confidence: 56%

Dendritic Cell–Derived Exosomes Need To Activate Both T and B Cells To Induce Antitumor Immunity

Näslund

Gehrmann

Qazi

et al. 2013

The Journal of Immunology

Self Cite

167

156

View full text Add to dashboard Cite

show abstract

“…Later, Ding et al (42) showed that targeting of Ags to B cells can potentiate specific T cell responses and break immune tolerance. Furthermore, B cells are particularly important in achieving long-term T cell immunity (43) and, recently, we showed that exosomes require the support of activated B cells for generating Ag-specific T cell responses in vivo (44). Hence, by targeting B cells in cancer vaccines, tolerance could be broken, and a more long-lasting T cell immunity might be achieved.…”

Section: Discussionmentioning

confidence: 99%

Exosomes Containing Glycoprotein 350 Released by EBV-Transformed B Cells Selectively Target B Cells through CD21 and Block EBV Infection In Vitro

Vallhov

Gutzeit

Johansson

et al. 2011

The Journal of Immunology

Self Cite

124

113

View full text Add to dashboard Cite

Exosomes are nano-sized membrane vesicles released from a wide variety of cells, formed in endosomes by inward budding of the endosomal limiting membrane. They have immune stimulatory-, inhibitory-, or tolerance-inducing effects, depending on their cellular origin, which is why they are investigated for use in vaccine and immune therapeutic strategies. In this study, we explored whether exosomes of different origins and functions can selectively target different immune cells in human peripheral blood. Flow cytometry, confocal laser scanning microscopy, and multispectral imaging flow cytometry (ImageStream) revealed that exosomes derived from human monocyte-derived dendritic cells and breast milk preferably associated with monocytes. In contrast, exosomes from an EBV-transformed B cell line (LCL1) preferentially targeted B cells. This was not observed for an EBV− B cell line (BJAB). Electron microscopy, size-distribution analysis (NanoSight), and a cord blood transformation assay excluded the presence of virions in our LCL1 exosome preparations. The interaction between LCL1-derived exosomes and peripheral blood B cells could be blocked efficiently by anti-CD21 or anti-gp350, indicating an interaction between CD21 on B cells and the EBV glycoprotein gp350 on exosomes. The targeting of LCL1-derived exosomes through gp350–CD21 interaction strongly inhibited EBV infection in B cells isolated from umbilical cord blood, suggesting a protective role for exosomes in regulating EBV infection. Our finding also suggests that exosome-based vaccines can be engineered for specific B cell targeting by inducing gp350 expression.

show abstract

“…Induction of exosomal release can be mediated via either cell activation or stress. 15) Recently, Aubertin et al 31) have reported that treatment of human prostate cancer cells with the cytotoxic agent DXR triggered a massive production of extracellular vesicles, including exosomes, both in vitro and in vivo in immunodeficient mice. In this study, we investigated the effect of DXR on serum exosomal protein level in conventional mice which hold whole immune system.…”

Section: Discussionmentioning

confidence: 99%

“…13) Dendritic cell-derived exosomes (dexosomes) eradicate tumors in a T cell-dependent and major histocompatibility complex (MHC)-restricted manner. 14,15) Exosome release is known to be triggered by various stimuli. Recently, many in vitro studies have demonstrated that exosomes are aggressively secreted by treatment with conventional anticancer drugs.…”

mentioning

confidence: 99%

Doxorubicin Expands <i>in Vivo</i> Secretion of Circulating Exosome in Mice

Emam

Ando

Lila

et al. 2018

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Modulation of tumor immunity is a known factor in the antitumor activity of many chemotherapeutic agents. Exosomes are extracellular nanometric vesicles that are released by almost all types of cells, which includes cancer cells. These vesicles play a crucial role in tumor immunity. Many in vitro studies have reproduced the aggressive secretion of exosomes following treatment with conventional anticancer drugs. Nevertheless, how chemotherapeutic agents including nanomedicines such as Doxil ® affect the in vivo secretion of exosomes is yet to be elucidated. In this study, the effect of intravenous injection of either free doxorubicin (DXR) or liposomal DXR formulation (Doxil ® ) on exosome secretion was evaluated in BALB/c mice. Exosomes were isolated from serum by using an ExoQuick kit. Free DXR treatment markedly increased serum exosome levels in a post-injection time-dependent manner, while Doxil ® treatment did not. Exosomal size distribution and marker protein expressions (CD9, CD63, and TSG101) were studied. The physical/biological characteristics of treatment-induced exosomes were comparable to those of control mice. Interestingly, splenectomy significantly suppressed the copious exosomal secretions induced by free DXR. Collectively, our results indicate that conventional anticancer agents induce the secretion of circulating exosomes, presumably via stimulating immune cells of the spleen. As far as we know, this study represents the first report indicating that conventional chemotherapeutics may induce exosome secretion which might, in turn, contribute partly to the antitumor effect of chemotherapeutic agents.

show abstract

Antigen-loaded exosomes alone induce Th1-type memory through a B cell–dependent mechanism

Cited by 204 publications

References 43 publications

Dendritic Cell–Derived Exosomes Need To Activate Both T and B Cells To Induce Antitumor Immunity

Dendritic Cell–Derived Exosomes Need To Activate Both T and B Cells To Induce Antitumor Immunity

Exosomes Containing Glycoprotein 350 Released by EBV-Transformed B Cells Selectively Target B Cells through CD21 and Block EBV Infection In Vitro

Doxorubicin Expands <i>in Vivo</i> Secretion of Circulating Exosome in Mice

Contact Info

Product

Resources

About