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Oncogenic JAK2causes PD-L1 expression, mediating immune escape in myeloproliferative neoplasms

Standard

Oncogenic JAK2causes PD-L1 expression, mediating immune escape in myeloproliferative neoplasms. / Prestipino, Alessandro; Emhardt, Alica J; Aumann, Konrad; O'Sullivan, David; Gorantla, Sivahari P; Duquesne, Sandra; Melchinger, Wolfgang; Braun, Lukas; Vuckovic, Slavica; Boerries, Melanie; Busch, Hauke; Halbach, Sebastian; Pennisi, Sandra; Poggio, Teresa; Apostolova, Petya; Veratti, Pia; Hettich, Michael; Niedermann, Gabriele; Bartholomä, Mark; Shoumariyeh, Khalid; Jutzi, Jonas S; Wehrle, Julius; Dierks, Christine; Becker, Heiko; Schmitt-Graeff, Annette; Follo, Marie; Pfeifer, Dietmar; Rohr, Jan; Fuchs, Sebastian; Ehl, Stephan; Hartl, Frederike A; Minguet, Susana; Miething, Cornelius; Heidel, Florian H; Kröger, Nicolaus; Triviai, Ioanna; Brummer, Tilman; Finke, Jürgen; Illert, Anna L; Ruggiero, Eliana; Bonini, Chiara; Duyster, Justus; Pahl, Heike L; Lane, Steven W; Hill, Geoffrey R; Blazar, Bruce R; von Bubnoff, Nikolas; Pearce, Erika L; Zeiser, Robert.

in: SCI TRANSL MED, Jahrgang 10, 21.02.2018, S. 429.

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

Harvard

Prestipino, A, Emhardt, AJ, Aumann, K, O'Sullivan, D, Gorantla, SP, Duquesne, S, Melchinger, W, Braun, L, Vuckovic, S, Boerries, M, Busch, H, Halbach, S, Pennisi, S, Poggio, T, Apostolova, P, Veratti, P, Hettich, M, Niedermann, G, Bartholomä, M, Shoumariyeh, K, Jutzi, JS, Wehrle, J, Dierks, C, Becker, H, Schmitt-Graeff, A, Follo, M, Pfeifer, D, Rohr, J, Fuchs, S, Ehl, S, Hartl, FA, Minguet, S, Miething, C, Heidel, FH, Kröger, N, Triviai, I, Brummer, T, Finke, J, Illert, AL, Ruggiero, E, Bonini, C, Duyster, J, Pahl, HL, Lane, SW, Hill, GR, Blazar, BR, von Bubnoff, N, Pearce, EL & Zeiser, R 2018, 'Oncogenic JAK2causes PD-L1 expression, mediating immune escape in myeloproliferative neoplasms', SCI TRANSL MED, Jg. 10, S. 429. https://doi.org/10.1126/scitranslmed.aam7729

APA

Prestipino, A., Emhardt, A. J., Aumann, K., O'Sullivan, D., Gorantla, S. P., Duquesne, S., Melchinger, W., Braun, L., Vuckovic, S., Boerries, M., Busch, H., Halbach, S., Pennisi, S., Poggio, T., Apostolova, P., Veratti, P., Hettich, M., Niedermann, G., Bartholomä, M., ... Zeiser, R. (2018). Oncogenic JAK2causes PD-L1 expression, mediating immune escape in myeloproliferative neoplasms. SCI TRANSL MED, 10, 429. https://doi.org/10.1126/scitranslmed.aam7729

Vancouver

Prestipino A, Emhardt AJ, Aumann K, O'Sullivan D, Gorantla SP, Duquesne S et al. Oncogenic JAK2causes PD-L1 expression, mediating immune escape in myeloproliferative neoplasms. SCI TRANSL MED. 2018 Feb 21;10:429. https://doi.org/10.1126/scitranslmed.aam7729

Bibtex

@article{aa821703c5934520aafbb098041154ee,
title = "Oncogenic JAK2causes PD-L1 expression, mediating immune escape in myeloproliferative neoplasms",
abstract = "Recent evidence has revealed that oncogenic mutations may confer immune escape. A better understanding of how an oncogenic mutation affects immunosuppressive programmed death ligand 1 (PD-L1) expression may help in developing new therapeutic strategies. We show that oncogenic JAK2 (Janus kinase 2) activity caused STAT3 (signal transducer and activator of transcription 3) and STAT5 phosphorylation, which enhanced PD-L1 promoter activity and PD-L1 protein expression in JAK2V617F-mutant cells, whereas blockade of JAK2 reduced PD-L1 expression in myeloid JAK2V617F-mutant cells. PD-L1 expression was higher on primary cells isolated from patients with JAK2V617F-myeloproliferative neoplasms (MPNs) compared to healthy individuals and declined upon JAK2 inhibition. JAK2V617Fmutational burden, pSTAT3, and PD-L1 expression were highest in primary MPN patient-derived monocytes, megakaryocytes, and platelets. PD-1 (programmed death receptor 1) inhibition prolonged survival in human MPN xenograft and primary murine MPN models. This effect was dependent on T cells. Mechanistically, PD-L1 surface expression in JAK2V617F-mutant cells affected metabolism and cell cycle progression of T cells. In summary, we report that in MPN, constitutive JAK2/STAT3/STAT5 activation, mainly in monocytes, megakaryocytes, and platelets, caused PD-L1-mediated immune escape by reducing T cell activation, metabolic activity, and cell cycle progression. The susceptibility of JAK2V617F-mutant MPN to PD-1 targeting paves the way for immunomodulatory approaches relying on PD-1 inhibition.",
keywords = "Journal Article",
author = "Alessandro Prestipino and Emhardt, {Alica J} and Konrad Aumann and David O'Sullivan and Gorantla, {Sivahari P} and Sandra Duquesne and Wolfgang Melchinger and Lukas Braun and Slavica Vuckovic and Melanie Boerries and Hauke Busch and Sebastian Halbach and Sandra Pennisi and Teresa Poggio and Petya Apostolova and Pia Veratti and Michael Hettich and Gabriele Niedermann and Mark Bartholom{\"a} and Khalid Shoumariyeh and Jutzi, {Jonas S} and Julius Wehrle and Christine Dierks and Heiko Becker and Annette Schmitt-Graeff and Marie Follo and Dietmar Pfeifer and Jan Rohr and Sebastian Fuchs and Stephan Ehl and Hartl, {Frederike A} and Susana Minguet and Cornelius Miething and Heidel, {Florian H} and Nicolaus Kr{\"o}ger and Ioanna Triviai and Tilman Brummer and J{\"u}rgen Finke and Illert, {Anna L} and Eliana Ruggiero and Chiara Bonini and Justus Duyster and Pahl, {Heike L} and Lane, {Steven W} and Hill, {Geoffrey R} and Blazar, {Bruce R} and {von Bubnoff}, Nikolas and Pearce, {Erika L} and Robert Zeiser",
note = "Copyright {\textcopyright} 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.",
year = "2018",
month = feb,
day = "21",
doi = "10.1126/scitranslmed.aam7729",
language = "English",
volume = "10",
pages = "429",
journal = "SCI TRANSL MED",
issn = "1946-6234",
publisher = "AMER ASSOC ADVANCEMENT SCIENCE",

}

RIS

TY - JOUR

T1 - Oncogenic JAK2causes PD-L1 expression, mediating immune escape in myeloproliferative neoplasms

AU - Prestipino, Alessandro

AU - Emhardt, Alica J

AU - Aumann, Konrad

AU - O'Sullivan, David

AU - Gorantla, Sivahari P

AU - Duquesne, Sandra

AU - Melchinger, Wolfgang

AU - Braun, Lukas

AU - Vuckovic, Slavica

AU - Boerries, Melanie

AU - Busch, Hauke

AU - Halbach, Sebastian

AU - Pennisi, Sandra

AU - Poggio, Teresa

AU - Apostolova, Petya

AU - Veratti, Pia

AU - Hettich, Michael

AU - Niedermann, Gabriele

AU - Bartholomä, Mark

AU - Shoumariyeh, Khalid

AU - Jutzi, Jonas S

AU - Wehrle, Julius

AU - Dierks, Christine

AU - Becker, Heiko

AU - Schmitt-Graeff, Annette

AU - Follo, Marie

AU - Pfeifer, Dietmar

AU - Rohr, Jan

AU - Fuchs, Sebastian

AU - Ehl, Stephan

AU - Hartl, Frederike A

AU - Minguet, Susana

AU - Miething, Cornelius

AU - Heidel, Florian H

AU - Kröger, Nicolaus

AU - Triviai, Ioanna

AU - Brummer, Tilman

AU - Finke, Jürgen

AU - Illert, Anna L

AU - Ruggiero, Eliana

AU - Bonini, Chiara

AU - Duyster, Justus

AU - Pahl, Heike L

AU - Lane, Steven W

AU - Hill, Geoffrey R

AU - Blazar, Bruce R

AU - von Bubnoff, Nikolas

AU - Pearce, Erika L

AU - Zeiser, Robert

N1 - Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

PY - 2018/2/21

Y1 - 2018/2/21

N2 - Recent evidence has revealed that oncogenic mutations may confer immune escape. A better understanding of how an oncogenic mutation affects immunosuppressive programmed death ligand 1 (PD-L1) expression may help in developing new therapeutic strategies. We show that oncogenic JAK2 (Janus kinase 2) activity caused STAT3 (signal transducer and activator of transcription 3) and STAT5 phosphorylation, which enhanced PD-L1 promoter activity and PD-L1 protein expression in JAK2V617F-mutant cells, whereas blockade of JAK2 reduced PD-L1 expression in myeloid JAK2V617F-mutant cells. PD-L1 expression was higher on primary cells isolated from patients with JAK2V617F-myeloproliferative neoplasms (MPNs) compared to healthy individuals and declined upon JAK2 inhibition. JAK2V617Fmutational burden, pSTAT3, and PD-L1 expression were highest in primary MPN patient-derived monocytes, megakaryocytes, and platelets. PD-1 (programmed death receptor 1) inhibition prolonged survival in human MPN xenograft and primary murine MPN models. This effect was dependent on T cells. Mechanistically, PD-L1 surface expression in JAK2V617F-mutant cells affected metabolism and cell cycle progression of T cells. In summary, we report that in MPN, constitutive JAK2/STAT3/STAT5 activation, mainly in monocytes, megakaryocytes, and platelets, caused PD-L1-mediated immune escape by reducing T cell activation, metabolic activity, and cell cycle progression. The susceptibility of JAK2V617F-mutant MPN to PD-1 targeting paves the way for immunomodulatory approaches relying on PD-1 inhibition.

AB - Recent evidence has revealed that oncogenic mutations may confer immune escape. A better understanding of how an oncogenic mutation affects immunosuppressive programmed death ligand 1 (PD-L1) expression may help in developing new therapeutic strategies. We show that oncogenic JAK2 (Janus kinase 2) activity caused STAT3 (signal transducer and activator of transcription 3) and STAT5 phosphorylation, which enhanced PD-L1 promoter activity and PD-L1 protein expression in JAK2V617F-mutant cells, whereas blockade of JAK2 reduced PD-L1 expression in myeloid JAK2V617F-mutant cells. PD-L1 expression was higher on primary cells isolated from patients with JAK2V617F-myeloproliferative neoplasms (MPNs) compared to healthy individuals and declined upon JAK2 inhibition. JAK2V617Fmutational burden, pSTAT3, and PD-L1 expression were highest in primary MPN patient-derived monocytes, megakaryocytes, and platelets. PD-1 (programmed death receptor 1) inhibition prolonged survival in human MPN xenograft and primary murine MPN models. This effect was dependent on T cells. Mechanistically, PD-L1 surface expression in JAK2V617F-mutant cells affected metabolism and cell cycle progression of T cells. In summary, we report that in MPN, constitutive JAK2/STAT3/STAT5 activation, mainly in monocytes, megakaryocytes, and platelets, caused PD-L1-mediated immune escape by reducing T cell activation, metabolic activity, and cell cycle progression. The susceptibility of JAK2V617F-mutant MPN to PD-1 targeting paves the way for immunomodulatory approaches relying on PD-1 inhibition.

KW - Journal Article

U2 - 10.1126/scitranslmed.aam7729

DO - 10.1126/scitranslmed.aam7729

M3 - SCORING: Journal article

C2 - 29467301

VL - 10

SP - 429

JO - SCI TRANSL MED

JF - SCI TRANSL MED

SN - 1946-6234

ER -