Mature dendritic cells pulsed with exosomes stimulate efficient cytotoxic T‐lymphocyte responses and antitumour immunity

Hao, Siguo; Bai, Ou; Li, Fang; Yuan, Jinkai; Laferté, Suzanne; Xiang, Jim

doi:10.1111/j.1365-2567.2006.02483.x

Cited by 213 publications

(235 citation statements)

References 45 publications

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“…The reasons might that: firstly, exosomes studied in most research were from pure DCs (35,36) or tumor cell lines (26,27,37,38). Exosomes from DCs have been identified to have the ability to activate immunological cells.…”

Section: The In Vitro Anti-ovarian Cancer Cytotoxic Activity Of the Pmentioning

confidence: 99%

Exosomes in the ascites of ovarian cancer patients: origin and effects on anti-tumor immunity

2011

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Abstract. This study was performed to identify the origin of the ascites-derived exosomes from patients with ovarian cancer and to observe the effect of exosomes on anti-tumor immunity. Exosomes were isolated from the ascites of patients with ovarian epithelial cancer by ultracentrifugation plus density gradient centrifugation. The origin of exosomes was identified by immunoelectronmicroscopy (IEM). The growth curve of the tumor cell line SKOV3 cultured with or without exosomes was analyzed. The apoptosis of autogeneic tumor cells (ATCs) and SKOV3 cells affected by exosomes was measured by flow cytometry (FCM) and light phase contrast microscopy. The cytotoxic effect of the peripheral blood mononuclear cells (PBMCs) stimulated by exosomes and/or dendritic cells (DCs) on ovarian cancer cells was measured using a CCK-8 assay. The levels of IFN-Á released by PBMCs stimulated by exosomes and/or DCs were measured by ELISA. The apoptosis of PBMCs and DCs affected by exosomes was measured by FCM and light microscopy. Whether the mature process of DCs was affected by exosomes was studied by FCM. The ratio of CD4 + T cell and CD8 + T cell were measured by FCM. FasL and TRAIL molecules on exosomes were detected by Western blot analysis. The human FasL antagonistic antibody was used to block the apoptosis of DCs and PBMCs induced by exosomes. The receptors of TRAIL DR4 and DR5 on PBMCs and DCs were detected by FCM. In 41 patients examined, we isolated exosomes from the ascites of 35 patients. We detected TCR, CD20, HLA-DR, B7-2, HER2/neu, CA125 and Histone H 2 A on exosomes. We found that exosomes might impair the cytotoxic activity of PBMCs when DCs are present. We found that exosomes had no effect on the growth and apoptosis of SKOV3 cells. However, exosomes may induce apoptosis of precursors, mature DCs and PBMCs. We found that FasL and TRAIL were present in the exosome suspension and addition of an anti-FasL antibody may decrease the percentage of apoptosis of DCs and PBMCs. We conclude that exosomes exist in ascites of 85.4% of patients with ovarian cancer. Moreover, these exosomes may be of multi-origin. Exosomes had no effect on the growth and apoptosis of tumor cells but impaired the cytotoxic activity of PBMCs in the presence of DCs. Exosomes also may induce apoptosis of the precursors of DCs, DCs and PBMCs. FasL and TRAIL on exosomes may partly account for the apoptosis of cells of the immune system.

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Section: The In Vitro Anti-ovarian Cancer Cytotoxic Activity Of the Pmentioning

confidence: 99%

Exosomes in the ascites of ovarian cancer patients: origin and effects on anti-tumor immunity

2011

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“…Exos are nanovesicles of endosomal source that contribute to the membrane traffic between different cell types [20,25]. In the immune system Exos were shown to transfer information and function from the cell that produced the Exos to those incorporating them [21][22]. Therefore, the actual incorporation of Exos from DCs by tumour cells, as shown here, opens new possibilities for immunotherapy, based on the use of such Exo-treated tumour cells as antigen-presenting cells of their own tumour antigens.…”

Section: Discussionmentioning

confidence: 99%

“…Actually, CD9, CD81, MHC-class I, T-cell receptors, CD54 and LFA-1 have been shown to affect the uptake of Exos by different cell types [22,25,[32][33][34]. Furthermore, mechanisms involved in this incorporation may vary among cell types and activation status both of target and source cells.…”

Section: Discussionmentioning

confidence: 99%

“…Exosomes are nanovesicles of 30-100nm of diameter that are released from cells as result from the fusion of multivesicular bodies (MVB) with the plasma membrane [18] and which are involved in intercellular communication in the body [19][20][21]. When originated from DCs, Exos contain many of the molecules involved in antigen presentation, are able to induce direct and indirect lymphocyte responses and can transfer MHC/peptides complex to other DCs [16][17][22][23].…”

Section: Introductionmentioning

confidence: 99%

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Tumour Cells Incorporate Exosomes Derived from Dendritic Cells Through a Mechanism Involving the Tetraspanin CD9

Romagnoli

Toniolo

Migliori

et al. 2013

Exosomes microvesicles

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Exosomes (Exos) are secreted nanovesicles that contain membrane proteins and genetic material, which can be transferred between cells and contribute to their communication in the body. We show that Exos, obtained from mature human dendritic cells (DCs), are incorporated by tumour cells, which after Exos treatment, acquire the expression of HLA-class I, HLA-class II, CD86, CD11c, CD54 and CD18. This incorporation reaches its peak eight hours after treatment, can be observed in different cell tumour lines (SK-BR-3, U87 and K562) and could be a means to transform non-immunogenic into immunogenic tumour cells. Interestingly, tetraspanins, which are expressed by the tumour cells, have their surface level decreased after Exo treatment. Furthermore, the intensity of Exo incorporation by the different tumour cell lines was proportional to their CD9 expression levels and pretreatment of Exos with anti-CD9 decreased their incorporation (by SK-BR-3 cells). This modification of tumour cells by DC-derived Exos may allow their use in new immunotherapeutic approaches to cancer. Furthermore, by showing the involvement of CD9 in this incorporation, we provide a possible selection criterion for tumours to be addressed by this strategy.

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“…Tumor cell-derived exosomes, which have been reported to contain tumor antigens and MHC class I molecules, can present tumor antigens to dendritic cells and induce CD8 + T-cell-dependent antitumor immune responses, leading to direct suppression of malignant tumor development. 76,77 Back in the 1990s, Raposo et al 78 have shown that the exosome-mediated fusion between MHC class II and the plasma membrane was the new pathway for antigen presentation. In the study of lymphomas, Chen et al 79 showed that exosomes released from heat-shocked mouse B lymphoma cells (HS-Exo) contain heat shock proteins (HSP) and numerous amounts of molecules involved in immunogenicity, including MHC class I, MHC class II, CD40, CD86, RANTES, and IL-1β.…”

Section: Lymphoma Exosomes Participate In Antitumor Effect and Immunementioning

confidence: 99%

Intimate cross-talk between cancer cells and the tumor microenvironment of B-cell lymphomas: The key role of exosomes

Wang

2017

Tumour Biol.

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B-cell lymphomas are composed of tumor cells and the tumor microenvironment, which is conventionally thought to be composed of a mixture of stromal cells, blood vessels, immune cells, and non-cell components, such as extracellular matrix, cytokines, and chemokines. Exosomes, small endocytically derived vesicles that have been proved to be present in a variety of tumor niches and involved in mediating cell signaling networks, are increasingly regarded as important components of tumor microenvironment. In this review, we first focus on the biogenesis, biodistribution, transportation, and other general characteristics of exosomes and then highlight the vital roles of exosomes in lymphomagenesis and disease progression, particularly from the perspective of immune dysfunction, virus infection, and therapeutic resistance mechanisms.

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Mature dendritic cells pulsed with exosomes stimulate efficient cytotoxic T‐lymphocyte responses and antitumour immunity

Cited by 213 publications

References 45 publications

Exosomes in the ascites of ovarian cancer patients: origin and effects on anti-tumor immunity

Exosomes in the ascites of ovarian cancer patients: origin and effects on anti-tumor immunity

Tumour Cells Incorporate Exosomes Derived from Dendritic Cells Through a Mechanism Involving the Tetraspanin CD9

Intimate cross-talk between cancer cells and the tumor microenvironment of B-cell lymphomas: The key role of exosomes

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