Exosomes from Plasmacytoma Cells as a Tumor Vaccine

Altieri, Stephen L; Khan, Andleeb; Tomasi, Thomas B.

doi:10.1097/00002371-200407000-00004

Cited by 85 publications

(51 citation statements)

References 22 publications

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“…Intracellular processing, which probably involves exosome-adhesion molecules (Clayton et al, 2004) that bind to the dendritic-cell surface before endocytosis and processing (Morelli et al, 2004), is certainly compatible with earlier studies documenting exosomes as antigen-deliveryvehicles to dendritic cells (Altieri et al, 2004;Andre et al, 2002;Wolfers et al, 2001). The relative potency of stressderived exosomes in such cross-presentation mechanisms is the subject of ongoing studies in our laboratory.…”

Section: Discussionsupporting

confidence: 76%

Induction of heat shock proteins in B-cell exosomes

Clayton

Turkes

Navabi

et al. 2005

Journal of Cell Science

403

314

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Exosomes are nanometer-sized vesicles secreted by a diverse range of live cells that probably have physiological roles in modulating cellular immunity. The extracellular factors that regulate the quantity and phenotype of exosomes produced are poorly understood, and the properties of exosomes that dictate their immune functions are not yet clear. We investigated the effect of cellular stress on the exosomes produced by B-lymphoblastoid cell lines. Under steady-state conditions, the exosomes were positive for hsp27, hsc70, hsp70 and hsp90, and other recognised exosome markers such as MHC class I, CD81, and LAMP-2. Exposing cells to heat stress (42°C for up to 3 hours), resulted in a marked increase in these heat shock proteins (hsps), while the expression of other stress proteins such as hsp60 and gp96 remained negative, and other exosome markers remained unchanged. Stress also triggered a small increase in the quantity of exosomes produced [with a ratio of 1.245±0.07 to 1 (mean±s.e.m., n=20) of 3-hour-stress-exosomes to control-exosomes]. Flow-cytometric analysis of exosome-coated beads and immuno-precipitation of intact exosomes demonstrated that hsps were located within the exosome lumen, and not present at the exosome-surface, suggesting that such exosomes may not interact with target cells through cell-surface hsp-receptors. Functional studies further supported this finding, in that exosomes from control or heat-stressed B cells did not trigger dendritic cell maturation, assessed by analysis of dendritic-cell-surface phenotype, and cytokine secretion profile. Our findings demonstrate that specific alterations in exosome phenotype are a hitherto unknown component of the cellular response to environmental stress and their extracellular function does not involve the direct activation of dendritic cells.

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Section: Discussionsupporting

confidence: 76%

Induction of heat shock proteins in B-cell exosomes

Clayton

Turkes

Navabi

et al. 2005

Journal of Cell Science

403

314

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“…Several studies have shown activation of immune responses by tumor exosomes, as prophylactic agents (40) or as therapeutic vaccines in murine cancer models (23) and in humans (11,41), usually by loading them onto enriched dendritic cell populations. By binding and endocytosing exosomes, dendritic cells may crosspresent exosome-delivered antigens to T cells and stimulate antitumor immunity (11,23).…”

Section: Discussionmentioning

confidence: 99%

Human Tumor-Derived Exosomes Selectively Impair Lymphocyte Responses to Interleukin-2

et al. 2007

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Exosomes are nanometer-sized vesicles, secreted by normal and neoplastic cells. The outcome following interaction between the cellular immune system and cancer-derived exosomes is not well understood. Interleukin-2 (IL-2) is a key factor supporting expansion and differentiation of CTL and natural killer (NK) cells but can also support regulatory T cells and their suppressive functions. Our study examined whether tumor-derived exosomes could modify lymphocyte IL-2 responses. Proliferation of healthy donor peripheral blood lymphocytes in response to IL-2 was inhibited by tumor exosomes. In unfractionated lymphocytes, this effect was seen in all cell subsets. Separating CD4 + T cells, CD8 + T cells, and NK cells revealed that CD8 + T-cell proliferation was not inhibited in the absence of CD4 + T cells and that NK cell proliferation was only slightly impaired. Other exosome effects included selective impairment of IL-2-mediated CD25 up-regulation, affecting all but the CD3 + CD8 À T-cell subset. IL-2-induced Foxp3 expression by CD4 + CD25 + cells was not inhibited by tumor exosomes, and the suppressive function of CD4 + CD25 + T cells was enhanced by exosomes. In contrast, exosomes directly inhibited NK cell killing function in a T-cell-independent manner. Analysis of tumor exosomes revealed membrane-associated transforming growth factor B 1 (TGFB 1 ), which contributed to the antiproliferative effects, shown by using neutralizing TGFB 1 -specific antibody. The data show an exosome-mediated mechanism of skewing IL-2 responsiveness in favor of regulatory T cells and away from cytotoxic cells. This coordinated ''double hit'' to cellular immunity strongly implicates the role of exosomes in tumor immune evasion. [Cancer Res 2007;67(15):7458-66]

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“…HSP70-80, Her2/Neu, Mart1, TRP and gp100 in melanoma, P1A (intracisternal A particle protein) and HSP70 in plasmacytoma cells. [79][80][81] However, these antitumor immune responses induced by TEXs are relatively weak and prone to induce tolerance. Therefore, these strategies are limited to in vitro observations and mouse model studies.…”

Section: Modified Tumor Cell-derived Exosomes (Texs)mentioning

confidence: 99%

The exosomes in tumor immunity

2015

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Exosomes are a kind of nanometric membrane vesicles and can be released by almost all kinds of cells, including cancer cells. As the important mediators in intercellular communications, exosomes mediate exchange of protein and genetic material derived from parental cells. Emerging evidences show that exosomes secreted by either host cells or cancer cells are involved in tumor initiation, growth, invasion and metastasis. Moreover, communications between immune cells and cancer cells via exosomes play dual roles in modulating tumor immunity. In this review, we focus on exosome-mediated immunosuppression via inhibition of antitumor responses elicited by immune cells (DCs, NK cells, CD4 C and CD8 C T cells, etc.) and induction of immunosuppressive or regulatory cell populations (MDSCs, Tregs and Bregs). Transfer of cytokines, microRNAs (miRNAs) and functional mRNAs by tumor-derived exosomes (TEXs) is crucial in the immune escape. Furthermore, exosomes secreted from several kinds of immune cells (DCs, CD4 C and CD8 C Tregs) also participate in immunosuppression. On the other hand, we summarize the current application of DCderived and modified tumor-derived exosomes as tumor vaccines. The potential challenges about exosome-based vaccines for clinical application are also discussed.

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Exosomes from Plasmacytoma Cells as a Tumor Vaccine

Cited by 85 publications

References 22 publications

Induction of heat shock proteins in B-cell exosomes

Induction of heat shock proteins in B-cell exosomes

Human Tumor-Derived Exosomes Selectively Impair Lymphocyte Responses to Interleukin-2

The exosomes in tumor immunity

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