Uptake of lymphoma-derived exosomes by peripheral blood leukocytes

Bennit, Heather R. Ferguson; Gonda, Amber; Oppegard, Laura; David, Poustka; Khan, Sharmin; Wall, Nathan R.

doi:10.2147/blctt.s130826

Cited by 13 publications

(12 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These heterogeneous protein profiles are specific to each cell type and contribute to the comparative ability of each cell to internalize exosomes. In line with the role of B cells, it was found that they readily take in exosomes, in contrast to other immune cells such as T cells and natural killer cells [61,64]. This suggests that certain immune cells are more effective at endocytosing exosomes than others, consistent with the primary functions of these specific cell types.…”

Section: Cell-specific Internalization Of Exosomes By Antigen Presentmentioning

confidence: 70%

“…In a peripheral blood mononuclear cell culture, when uptake by monocytes was blocked, internalization by T-cells increased [47], suggesting that T cell uptake may be an adaptive response to increased exosome concentration. When exosome uptake was compared to multiple splenic leukocytes [15] or peripheral blood leukocytes [64], T cells showed minimal internalization. T cell activity is often regulated by surface interactions with other cells, such as with the T cell receptor and the MHC II/antigen interaction with APCs.…”

Section: Circulating Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Cellular-Defined Microenvironmental Internalization of Exosomes

Gonda¹,

Moyron²,

Kabagwira³

et al. 2020

Extracellular Vesicles and Their Importance in Human Health

Self Cite

View full text Add to dashboard Cite

The extracellular environment exhibits a potent effect on cellular growth and development. Exosomes secreted into this milieu carry functional proteins and nucleic acids from the cell of origin to recipient cells, facilitating intercellular communication. This interaction is particularly influential in the tumor microenvironment, transporting oncogenes and oncoproteins within a tumor and to distant sites. The mechanisms by which cells internalize exosomes vary greatly and the factors dictating this process are still unknown. Most cancers show evidence of exosomal transfer of material, but differences in cell type can dictate the effectiveness and extent of the process. Improving therapeutics requires addressing specific cellular functions, illustrating the need to better understand the forces involved in exosome-cell interactions. This review summarizes what is known about the different types of cells that play a role in exosome internalization.

show abstract

Section: Cell-specific Internalization Of Exosomes By Antigen Presentmentioning

confidence: 70%

Section: Circulating Cellsmentioning

confidence: 99%

Cellular-Defined Microenvironmental Internalization of Exosomes

Gonda¹,

Moyron²,

Kabagwira³

et al. 2020

Extracellular Vesicles and Their Importance in Human Health

Self Cite

View full text Add to dashboard Cite

show abstract

“…Exosomes were then re-assessed for size and concentration and no alteration to size was observed (data not shown). Exosome uptake has been described to take as little as 1 hour up to 12 hours, with a general plateau effect at 4 hours [ 39 , 47 – 49 ]. HeLa cells were incubated with these exosomes for 4 hours and then analyzed with flow cytometry or with fluorescent microscopy (Figures 2 - 7 ).…”

Section: Resultsmentioning

confidence: 99%

Exosomal survivin facilitates vesicle internalization

et al. 2018

Self Cite

View full text Add to dashboard Cite

Survivin, a member of the inhibitor of apoptosis (IAP) protein family plays a significant role in cell fate and function. It is significantly overexpressed in tumor cells and has been identified in most cancer cell types. A novel extracellular population has recently been identified and its function is still unknown. Emerging evidence continues to shed light on the important role the tumor microenvironment (TME) has on tumor survival and progression. This new population of survivin has been seen to enhance the tumor phenotype when internalized by recipient cells. In this paper, we sought to better understand the mechanism by which survivin is taken up by cancer cells and the possible role it plays in this phenomenon. We isolated the exosomal carriers of extracellular survivin and using a lipophilic stain, PKH67, we tracked their uptake with immunofluorescence and flow cytometry. We found that by blocking exosomal survivin, exosome internalization is reduced, signifying a novel function for this protein. We also discovered that the common membrane receptors, transferrin receptor, endothelin B receptor, insulin receptor alpha, and membrane glucocorticoid receptor all facilitate exosomal internalization. This understanding further clarifies the protein-protein interactions in the TME that may influence tumor progression and identifies additional potential chemotherapeutic targets.

show abstract

“…While an effect on NK cell protein was seen with survivin by itself, the effect was lost by dilution into exosomes. Therefore, survivin in the TME sourced from necrosing tumor cells may show more effects than exosomal survivin due either to concentration or uptake issues, as NK cells have not been shown to efficiently uptake exosomes [ 47 ].…”

Section: Discussionmentioning

confidence: 99%

“…Natural killer (NK) cells were prepared from freshly collected plasma apheresis peripheral blood obtained from healthy donors at the Life Stream Blood Bank (San Bernardino, CA, USA), in accordance with Loma Linda University IRB protocols. Peripheral blood was prepared as described previously [ 47 ]. NK cells were obtained from the total lymphocyte fraction by negative immunomagnetic cell separation using either EasySep or RosetteSep negative selection kit (STEMCELL, Vancouver, BC, USA) or MACS magnetic NK cell isolation kit (Miltenyi Biotec, Auburn, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Natural Killer Cell Phenotype and Functionality Affected by Exposure to Extracellular Survivin and Lymphoma-Derived Exosomes

Bennit

Gonda

Kabagwira

et al. 2021

IJMS

Self Cite

View full text Add to dashboard Cite

The inherent abilities of natural killer (NK) cells to recognize and kill target cells place them among the first cells with the ability to recognize and destroy infected or transformed cells. Cancer cells, however, have mechanisms by which they can inhibit the surveillance and cytotoxic abilities of NK cells with one believed mechanism for this: their ability to release exosomes. Exosomes are vesicles that are found in abundance in the tumor microenvironment that can modulate intercellular communication and thus enhance tumor malignancy. Recently, our lab has found cancer cell exosomes to contain the inhibitor of apoptosis (IAP) protein survivin to be associated with decreased immune response in lymphocytes and cellular death. The purpose of this study was to explore the effect of survivin and lymphoma-derived survivin-containing exosomes on the immune functions of NK cells. NK cells were obtained from the peripheral blood of healthy donors and treated with pure survivin protein or exosomes from two lymphoma cell lines, DLCL2 and FSCCL. RNA was isolated from NK cell samples for measurement by PCR, and intracellular flow cytometry was used to determine protein expression. Degranulation capacity, cytotoxicity, and natural killer group 2D receptor (NKG2D) levels were also assessed. Lymphoma exosomes were examined for size and protein content. This study established that these lymphoma exosomes contained survivin and FasL but were negative for MHC class I-related chains (MIC)/B (MICA/B) and TGF-β. Treatment with exosomes did not significantly alter NK cell functionality, but extracellular survivin was seen to decrease natural killer group 2D receptor (NKG2D) levels and the intracellular protein levels of perforin, granzyme B, TNF-α, and IFN-γ.

show abstract

Uptake of lymphoma-derived exosomes by peripheral blood leukocytes

Cited by 13 publications

References 62 publications

Cellular-Defined Microenvironmental Internalization of Exosomes

Cellular-Defined Microenvironmental Internalization of Exosomes

Exosomal survivin facilitates vesicle internalization

Natural Killer Cell Phenotype and Functionality Affected by Exposure to Extracellular Survivin and Lymphoma-Derived Exosomes

Contact Info

Product

Resources

About