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Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles

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Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles. / Ricklefs, Franz Lennard; Alayo, Quazim; Krenzlin, Harald; Mahmoud, Ahmad; Speranza, Marica; Nakashima, Hiroshi; Hayes, Josie; Lee, Kyungheon; Balaj, Leonora; Passaro, Carmela; Krasemann, Susanne; Carter, Bob; Chen, Clark; Steed, Tyler; Treiber, Jeffrey; Rodig, Scott; Yang, Katherine; Nakano, Ichiro; Lee, Hakho; Weissleder, Ralph; Breakefield, Xandra; Godlweski, Jakub; Westphal, Manfred; Lamszus, Katrin; Freeman, Gordon; Bronisz, Agnieszka; Lawler, Sean; Chiocca, E Antonio.

in: SCI ADV, Jahrgang 4, Nr. 3, 03.2018, S. eaar2766.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Ricklefs, FL, Alayo, Q, Krenzlin, H, Mahmoud, A, Speranza, M, Nakashima, H, Hayes, J, Lee, K, Balaj, L, Passaro, C, Krasemann, S, Carter, B, Chen, C, Steed, T, Treiber, J, Rodig, S, Yang, K, Nakano, I, Lee, H, Weissleder, R, Breakefield, X, Godlweski, J, Westphal, M, Lamszus, K, Freeman, G, Bronisz, A, Lawler, S & Chiocca, EA 2018, 'Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles', SCI ADV, Jg. 4, Nr. 3, S. eaar2766. https://doi.org/10.1126/sciadv.aar2766

APA

Ricklefs, F. L., Alayo, Q., Krenzlin, H., Mahmoud, A., Speranza, M., Nakashima, H., Hayes, J., Lee, K., Balaj, L., Passaro, C., Krasemann, S., Carter, B., Chen, C., Steed, T., Treiber, J., Rodig, S., Yang, K., Nakano, I., Lee, H., ... Chiocca, E. A. (2018). Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles. SCI ADV, 4(3), eaar2766. https://doi.org/10.1126/sciadv.aar2766

Vancouver

Ricklefs FL, Alayo Q, Krenzlin H, Mahmoud A, Speranza M, Nakashima H et al. Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles. SCI ADV. 2018 Mär;4(3):eaar2766. https://doi.org/10.1126/sciadv.aar2766

Bibtex

@article{4bb43f9868bf43a894117482054cfb84,
title = "Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles",
abstract = "Binding of programmed death ligand-1 (PD-L1) to programmed cell death protein-1 (PD1) leads to cancer immune evasion via inhibition of T cell function. One of the defining characteristics of glioblastoma, a universally fatal brain cancer, is its profound local and systemic immunosuppression. Glioblastoma has also been shown to generate extracellular vesicles (EVs), which may play an important role in tumor progression. We thus hypothesized that glioblastoma EVs may be important mediators of immunosuppression and that PD-L1 could play a role. We show that glioblastoma EVs block T cell activation and proliferation in response to T cell receptor stimulation. PD-L1 was expressed on the surface of some, but not of all, glioblastoma-derived EVs, with the potential to directly bind to PD1. An anti-PD1 receptor blocking antibody significantly reversed the EV-mediated blockade of T cell activation but only when PD-L1 was present on EVs. When glioblastoma PD-L1 was up-regulated by IFN-γ, EVs also showed some PD-L1-dependent inhibition of T cell activation. PD-L1 expression correlated with the mesenchymal transcriptome profile and was anatomically localized in the perinecrotic and pseudopalisading niche of human glioblastoma specimens. PD-L1 DNA was present in circulating EVs from glioblastoma patients where it correlated with tumor volumes of up to 60 cm3. These results suggest that PD-L1 on EVs may be another mechanism for glioblastoma to suppress antitumor immunity and support the potential of EVs as biomarkers in tumor patients.",
author = "Ricklefs, {Franz Lennard} and Quazim Alayo and Harald Krenzlin and Ahmad Mahmoud and Marica Speranza and Hiroshi Nakashima and Josie Hayes and Kyungheon Lee and Leonora Balaj and Carmela Passaro and Susanne Krasemann and Bob Carter and Clark Chen and Tyler Steed and Jeffrey Treiber and Scott Rodig and Katherine Yang and Ichiro Nakano and Hakho Lee and Ralph Weissleder and Xandra Breakefield and Jakub Godlweski and Manfred Westphal and Katrin Lamszus and Gordon Freeman and Agnieszka Bronisz and Sean Lawler and Chiocca, {E Antonio}",
year = "2018",
month = mar,
doi = "10.1126/sciadv.aar2766",
language = "English",
volume = "4",
pages = "eaar2766",
journal = "SCI ADV",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "3",

}

RIS

TY - JOUR

T1 - Immune evasion mediated by PD-L1 on glioblastoma-derived extracellular vesicles

AU - Ricklefs, Franz Lennard

AU - Alayo, Quazim

AU - Krenzlin, Harald

AU - Mahmoud, Ahmad

AU - Speranza, Marica

AU - Nakashima, Hiroshi

AU - Hayes, Josie

AU - Lee, Kyungheon

AU - Balaj, Leonora

AU - Passaro, Carmela

AU - Krasemann, Susanne

AU - Carter, Bob

AU - Chen, Clark

AU - Steed, Tyler

AU - Treiber, Jeffrey

AU - Rodig, Scott

AU - Yang, Katherine

AU - Nakano, Ichiro

AU - Lee, Hakho

AU - Weissleder, Ralph

AU - Breakefield, Xandra

AU - Godlweski, Jakub

AU - Westphal, Manfred

AU - Lamszus, Katrin

AU - Freeman, Gordon

AU - Bronisz, Agnieszka

AU - Lawler, Sean

AU - Chiocca, E Antonio

PY - 2018/3

Y1 - 2018/3

N2 - Binding of programmed death ligand-1 (PD-L1) to programmed cell death protein-1 (PD1) leads to cancer immune evasion via inhibition of T cell function. One of the defining characteristics of glioblastoma, a universally fatal brain cancer, is its profound local and systemic immunosuppression. Glioblastoma has also been shown to generate extracellular vesicles (EVs), which may play an important role in tumor progression. We thus hypothesized that glioblastoma EVs may be important mediators of immunosuppression and that PD-L1 could play a role. We show that glioblastoma EVs block T cell activation and proliferation in response to T cell receptor stimulation. PD-L1 was expressed on the surface of some, but not of all, glioblastoma-derived EVs, with the potential to directly bind to PD1. An anti-PD1 receptor blocking antibody significantly reversed the EV-mediated blockade of T cell activation but only when PD-L1 was present on EVs. When glioblastoma PD-L1 was up-regulated by IFN-γ, EVs also showed some PD-L1-dependent inhibition of T cell activation. PD-L1 expression correlated with the mesenchymal transcriptome profile and was anatomically localized in the perinecrotic and pseudopalisading niche of human glioblastoma specimens. PD-L1 DNA was present in circulating EVs from glioblastoma patients where it correlated with tumor volumes of up to 60 cm3. These results suggest that PD-L1 on EVs may be another mechanism for glioblastoma to suppress antitumor immunity and support the potential of EVs as biomarkers in tumor patients.

AB - Binding of programmed death ligand-1 (PD-L1) to programmed cell death protein-1 (PD1) leads to cancer immune evasion via inhibition of T cell function. One of the defining characteristics of glioblastoma, a universally fatal brain cancer, is its profound local and systemic immunosuppression. Glioblastoma has also been shown to generate extracellular vesicles (EVs), which may play an important role in tumor progression. We thus hypothesized that glioblastoma EVs may be important mediators of immunosuppression and that PD-L1 could play a role. We show that glioblastoma EVs block T cell activation and proliferation in response to T cell receptor stimulation. PD-L1 was expressed on the surface of some, but not of all, glioblastoma-derived EVs, with the potential to directly bind to PD1. An anti-PD1 receptor blocking antibody significantly reversed the EV-mediated blockade of T cell activation but only when PD-L1 was present on EVs. When glioblastoma PD-L1 was up-regulated by IFN-γ, EVs also showed some PD-L1-dependent inhibition of T cell activation. PD-L1 expression correlated with the mesenchymal transcriptome profile and was anatomically localized in the perinecrotic and pseudopalisading niche of human glioblastoma specimens. PD-L1 DNA was present in circulating EVs from glioblastoma patients where it correlated with tumor volumes of up to 60 cm3. These results suggest that PD-L1 on EVs may be another mechanism for glioblastoma to suppress antitumor immunity and support the potential of EVs as biomarkers in tumor patients.

U2 - 10.1126/sciadv.aar2766

DO - 10.1126/sciadv.aar2766

M3 - SCORING: Journal article

C2 - 29532035

VL - 4

SP - eaar2766

JO - SCI ADV

JF - SCI ADV

SN - 2375-2548

IS - 3

ER -