Immune landscapes predict chemotherapy resistance and immunotherapy response in acute myeloid leukemia

Jayakumar Vadakekolathu; Mark D. Minden; Tressa Hood; Sarah E. Church; Stephen Reeder; Heidi Altmann; Amy H. Sullivan; Elena J. Viboch; Tasleema Patel; Narmin Ibrahimova; Sarah E. Warren; Andrea Arruda; Yan Liang; Thomas H. Smith; Gemma A. Foulds; Michael D. Bailey; James Gowen-MacDonald; John Muth; Marc Schmitz; Alessandra Cesano; A. Graham Pockley; Peter J.M. Valk; Bob Löwenberg; Martin Bornhäuser; Sarah K. Tasian; Michael P. Rettig; Jan K. Davidson-Moncada; John F. DiPersio; Sergio Rutella

doi:10.1126/scitranslmed.aaz0463

Immune landscapes predict chemotherapy resistance and immunotherapy response in acute myeloid leukemia

Jayakumar Vadakekolathu, Mark D. Minden, Tressa Hood, Sarah E. Church, Stephen Reeder, Heidi Altmann, Amy H. Sullivan, Elena J. Viboch, Tasleema Patel, Narmin Ibrahimova, Sarah E. Warren, Andrea Arruda, Yan Liang, Thomas H. Smith, Gemma A. Foulds, Michael D. Bailey, James Gowen-MacDonald, John Muth, Marc Schmitz, Alessandra CesanoA. Graham Pockley, Peter J.M. Valk, Bob Löwenberg, Martin Bornhäuser, Sarah K. Tasian, Michael P. Rettig, Jan K. Davidson-Moncada, John F. DiPersio, Sergio Rutella

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Abstract

Acute myeloid leukemia (AML) is a molecularly and clinically heterogeneous hematological malignancy. Although immunotherapy may be an attractive modality to exploit in patients with AML, the ability to predict the groups of patients and the types of cancer that will respond to immune targeting remains limited. This study dissected the complexity of the immune architecture of AML at high resolution and assessed its influence on therapeutic response. Using 442 primary bone marrow samples from three independent cohorts of children and adults with AML, we defined immune-infiltrated and immune-depleted disease classes and revealed critical differences in immune gene expression across age groups and molecular disease subtypes. Interferon (IFN)–γ–related mRNA profiles were predictive for both chemotherapy resistance and response of primary refractory/relapsed AML to flotetuzumab immunotherapy. Our compendium of microenvironmental gene and protein profiles provides insights into the immuno-biology of AML and could inform the delivery of personalized immunotherapies to IFN-γ–dominant AML subtypes.

Original language	English
Article number	eaaz0463
Journal	Science translational medicine
Volume	12
Issue number	546
DOIs	https://doi.org/10.1126/scitranslmed.aaz0463
State	Published - Jun 3 2020

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Vadakekolathu, J., Minden, M. D., Hood, T., Church, S. E., Reeder, S., Altmann, H., Sullivan, A. H., Viboch, E. J., Patel, T., Ibrahimova, N., Warren, S. E., Arruda, A., Liang, Y., Smith, T. H., Foulds, G. A., Bailey, M. D., Gowen-MacDonald, J., Muth, J., Schmitz, M., ... Rutella, S. (2020). Immune landscapes predict chemotherapy resistance and immunotherapy response in acute myeloid leukemia. Science translational medicine, 12(546), Article eaaz0463. https://doi.org/10.1126/scitranslmed.aaz0463

@article{913ea3511301482c87f5577701c36f7e,

title = "Immune landscapes predict chemotherapy resistance and immunotherapy response in acute myeloid leukemia",

abstract = "Acute myeloid leukemia (AML) is a molecularly and clinically heterogeneous hematological malignancy. Although immunotherapy may be an attractive modality to exploit in patients with AML, the ability to predict the groups of patients and the types of cancer that will respond to immune targeting remains limited. This study dissected the complexity of the immune architecture of AML at high resolution and assessed its influence on therapeutic response. Using 442 primary bone marrow samples from three independent cohorts of children and adults with AML, we defined immune-infiltrated and immune-depleted disease classes and revealed critical differences in immune gene expression across age groups and molecular disease subtypes. Interferon (IFN)–γ–related mRNA profiles were predictive for both chemotherapy resistance and response of primary refractory/relapsed AML to flotetuzumab immunotherapy. Our compendium of microenvironmental gene and protein profiles provides insights into the immuno-biology of AML and could inform the delivery of personalized immunotherapies to IFN-γ–dominant AML subtypes.",

author = "Jayakumar Vadakekolathu and Minden, {Mark D.} and Tressa Hood and Church, {Sarah E.} and Stephen Reeder and Heidi Altmann and Sullivan, {Amy H.} and Viboch, {Elena J.} and Tasleema Patel and Narmin Ibrahimova and Warren, {Sarah E.} and Andrea Arruda and Yan Liang and Smith, {Thomas H.} and Foulds, {Gemma A.} and Bailey, {Michael D.} and James Gowen-MacDonald and John Muth and Marc Schmitz and Alessandra Cesano and Pockley, {A. Graham} and Valk, {Peter J.M.} and Bob L{\"o}wenberg and Martin Bornh{\"a}user and Tasian, {Sarah K.} and Rettig, {Michael P.} and Davidson-Moncada, {Jan K.} and DiPersio, {John F.} and Sergio Rutella",

note = "Publisher Copyright: Copyright {\textcopyright} 2020 The Authors, some rights reserved.",

year = "2020",

month = jun,

day = "3",

doi = "10.1126/scitranslmed.aaz0463",

language = "English",

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Vadakekolathu, J, Minden, MD, Hood, T, Church, SE, Reeder, S, Altmann, H, Sullivan, AH, Viboch, EJ, Patel, T, Ibrahimova, N, Warren, SE, Arruda, A, Liang, Y, Smith, TH, Foulds, GA, Bailey, MD, Gowen-MacDonald, J, Muth, J, Schmitz, M, Cesano, A, Pockley, AG, Valk, PJM, Löwenberg, B, Bornhäuser, M, Tasian, SK, Rettig, MP, Davidson-Moncada, JK, DiPersio, JF & Rutella, S 2020, 'Immune landscapes predict chemotherapy resistance and immunotherapy response in acute myeloid leukemia', Science translational medicine, vol. 12, no. 546, eaaz0463. https://doi.org/10.1126/scitranslmed.aaz0463

TY - JOUR

T1 - Immune landscapes predict chemotherapy resistance and immunotherapy response in acute myeloid leukemia

AU - Vadakekolathu, Jayakumar

AU - Minden, Mark D.

AU - Hood, Tressa

AU - Church, Sarah E.

AU - Reeder, Stephen

AU - Altmann, Heidi

AU - Sullivan, Amy H.

AU - Viboch, Elena J.

AU - Patel, Tasleema

AU - Ibrahimova, Narmin

AU - Warren, Sarah E.

AU - Arruda, Andrea

AU - Liang, Yan

AU - Smith, Thomas H.

AU - Foulds, Gemma A.

AU - Bailey, Michael D.

AU - Gowen-MacDonald, James

AU - Muth, John

AU - Schmitz, Marc

AU - Cesano, Alessandra

AU - Pockley, A. Graham

AU - Valk, Peter J.M.

AU - Löwenberg, Bob

AU - Bornhäuser, Martin

AU - Tasian, Sarah K.

AU - Rettig, Michael P.

AU - Davidson-Moncada, Jan K.

AU - DiPersio, John F.

AU - Rutella, Sergio

PY - 2020/6/3

Y1 - 2020/6/3

N2 - Acute myeloid leukemia (AML) is a molecularly and clinically heterogeneous hematological malignancy. Although immunotherapy may be an attractive modality to exploit in patients with AML, the ability to predict the groups of patients and the types of cancer that will respond to immune targeting remains limited. This study dissected the complexity of the immune architecture of AML at high resolution and assessed its influence on therapeutic response. Using 442 primary bone marrow samples from three independent cohorts of children and adults with AML, we defined immune-infiltrated and immune-depleted disease classes and revealed critical differences in immune gene expression across age groups and molecular disease subtypes. Interferon (IFN)–γ–related mRNA profiles were predictive for both chemotherapy resistance and response of primary refractory/relapsed AML to flotetuzumab immunotherapy. Our compendium of microenvironmental gene and protein profiles provides insights into the immuno-biology of AML and could inform the delivery of personalized immunotherapies to IFN-γ–dominant AML subtypes.

AB - Acute myeloid leukemia (AML) is a molecularly and clinically heterogeneous hematological malignancy. Although immunotherapy may be an attractive modality to exploit in patients with AML, the ability to predict the groups of patients and the types of cancer that will respond to immune targeting remains limited. This study dissected the complexity of the immune architecture of AML at high resolution and assessed its influence on therapeutic response. Using 442 primary bone marrow samples from three independent cohorts of children and adults with AML, we defined immune-infiltrated and immune-depleted disease classes and revealed critical differences in immune gene expression across age groups and molecular disease subtypes. Interferon (IFN)–γ–related mRNA profiles were predictive for both chemotherapy resistance and response of primary refractory/relapsed AML to flotetuzumab immunotherapy. Our compendium of microenvironmental gene and protein profiles provides insights into the immuno-biology of AML and could inform the delivery of personalized immunotherapies to IFN-γ–dominant AML subtypes.

UR - http://www.scopus.com/inward/record.url?scp=85086007826&partnerID=8YFLogxK

U2 - 10.1126/scitranslmed.aaz0463

DO - 10.1126/scitranslmed.aaz0463

M3 - Article

C2 - 32493790

AN - SCOPUS:85086007826

SN - 1946-6234

VL - 12

JO - Science translational medicine

JF - Science translational medicine

IS - 546

M1 - eaaz0463

ER -

Immune landscapes predict chemotherapy resistance and immunotherapy response in acute myeloid leukemia

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