CD20 expression, TrkB activation and functional activity of diffuse large B cell lymphoma-derived small extracellular vesicles

Aitamer, Marine; Akil, Hussein; Vignoles, Chantal; Branchaud, Maud; Abraham, Julie; Gachard, Nathalie; Feuillard, Jean; Jauberteau, Marie-Odile; Shirvani, Hamasseh; Troutaud, Danielle; Bentayeb, Hafidha

doi:10.1038/s41416-021-01611-7

Cited by 3 publications

(3 citation statements)

References 42 publications

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“…1D, E). As we previously reported for CD20 [9], PD-L1 level was not related to the DLBCL subtype, but seemed reflect that of parental cells (Fig. 1B, C, E).…”

Section: To the Editorsupporting

confidence: 75%

“…Interestingly, they may also contribute to drug resistance. We have previously analyzed CD20 levels on sEV derived from ABC and GCB DLBCL cell lines, and demonstrated in a preclinical model sEV role in protecting tumors from the rituximab cytotoxicity [9]. However, heterogeneity of CD20 level on circulating sEV has not been evaluated in patients.…”

Section: To the Editormentioning

confidence: 99%

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Analysis of CD20 and PD-L1 levels on small extracellular vesicles (sEV) produced by DLBCL cells and EBV-transformed B cells, and potential role in T cell inhibition

Akil,

Bentayeb,

Aitamer

et al. 2024

Exp Hematol Oncol

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Increasing evidence supports a role for small extracellular vesicles (sEV, including exosomes) in Diffuse Large B-cell lymphoma (DLBCL) progression and resistance to treatment. CD20 and PD-L1 are found on DLBCL-derived sEV, but little is known about their patient-level heterogeneity. Moreover, the capacity of PD-L1+ sEV to modulate T cells needs to be clarified. Herein we analyzed sEV produced by human DLBCL cell lines and EBV-transformed B cell-lymphoblastoid cell lines (LCLs), a model allowing autologous T cell co-cultures. We determined CD20 and PD-L1 levels on plasma sEV from patient samples vs healthy volunteers (HV). sEV functional relevance was also investigated on CD4+ and CD8+ T cells. sEV derived from all cell lines showed an enrichment of CD20 and a high glycosylated PD-L1 expression when compared to cell lysates. High PD-L1 expression on LCL-derived sEV was associated with higher CD4+ and CD8+ T cell apoptosis. In patients, plasma sEV concentration was higher vs HV. Compared to sEV-CD20 level that seemed higher in patients, PD-L1 level in sEV was not different from those of HV. A high glycosylated PD-L1 level was shown in sEV from both patients and HV plasma samples, that was associated with the same inhibiting effect on activated T cells. We conclude that sEV derived from EBV-transformed B cells realize an immunosuppressive role that involved cell–cell interaction and probably at least PD-L1. Furthermore, our findings suggest the potential of circulating sEV as a source of biomarkers in DLBCL, notably to have information on immunotherapeutic target levels of parental tumor cells.

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“…1D, E). As we previously reported for CD20 [9], PD-L1 level was not related to the DLBCL subtype, but seemed reflect that of parental cells (Fig. 1B, C, E).…”

Section: To the Editorsupporting

confidence: 75%

Section: To the Editormentioning

confidence: 99%

Analysis of CD20 and PD-L1 levels on small extracellular vesicles (sEV) produced by DLBCL cells and EBV-transformed B cells, and potential role in T cell inhibition

Akil,

Bentayeb,

Aitamer

et al. 2024

Exp Hematol Oncol

Self Cite

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show abstract

“…HER-2-positive exosomes from cell culture and breast cancer patients have been shown to express active fulllength HER-2 and bind to Trastuzumab, inhibiting its activity [223]. A similar mechanism was observed in B-cell lymphoma, where CD20-expressing exosomes function as a decoy for Rituximab [224,225]. In a colon cancer model, exosomes could transfer cetuximab resistance to sensitive cells by downregulating PTEN and increasing p-Akt levels [226].…”

Section: Immunotherapy and Targeted Therapymentioning

confidence: 83%

Exosomes in Cancer Progression and Therapy Resistance: Molecular Insights and Therapeutic Opportunities

Wandrey,

Jablonska,

Stauber

et al. 2023

Life

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The development of therapy resistance still represents a major hurdle in treating cancers, leading to impaired treatment success and increased patient morbidity. The establishment of minimally invasive liquid biopsies is a promising approach to improving the early diagnosis, as well as therapy monitoring, of solid tumors. Because of their manifold functions in the tumor microenvironment, tumor-associated small extracellular vesicles, referred to as exosomes, have become a subject of intense research. Besides their important roles in cancer progression, metastasis, and the immune response, it has been proposed that exosomes also contribute to the acquisition and transfer of therapy resistance, mainly by delivering functional proteins and RNAs, as well as facilitating the export of active drugs or functioning as extracellular decoys. Extensive research has focused on understanding the molecular mechanisms underlying the occurrence of resistance and translating these into strategies for early detection. With this review, we want to provide an overview of the current knowledge about the (patho-)biology of exosomes, as well as state-of-the-art methods of isolation and analysis. Furthermore, we highlight the role of exosomes in tumorigenesis and cancer treatment, where they can function as therapeutic agents, biomarkers, and/or targets. By focusing on their roles in therapy resistance, we will reveal new paths of exploiting exosomes for cancer diagnosis and treatment.

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Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells via TGF-β signaling

Hao,

Chen,

Guo

et al. 2023

Front. Med.

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CD20 expression, TrkB activation and functional activity of diffuse large B cell lymphoma-derived small extracellular vesicles

Cited by 3 publications

References 42 publications

Analysis of CD20 and PD-L1 levels on small extracellular vesicles (sEV) produced by DLBCL cells and EBV-transformed B cells, and potential role in T cell inhibition

Analysis of CD20 and PD-L1 levels on small extracellular vesicles (sEV) produced by DLBCL cells and EBV-transformed B cells, and potential role in T cell inhibition

Exosomes in Cancer Progression and Therapy Resistance: Molecular Insights and Therapeutic Opportunities

Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells via TGF-β signaling

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