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

被引：154

作者：

Vadakekolathu, Jayakumar ^{[1
]}

Minden, Mark D. ^{[2
]}

Hood, Tressa ^{[3
]}

Church, Sarah E. ^{[3
]}

Reeder, Stephen ^{[1
]}

Altmann, Heidi ^{[4
]}

Sullivan, Amy H. ^{[3
]}

Viboch, Elena J. ^{[3
]}

Patel, Tasleema ^{[5
,6
,7
]}

Ibrahimova, Narmin ^{[2
]}

Warren, Sarah E. ^{[3
]}

Arruda, Andrea ^{[2
]}

Liang, Yan ^{[3
]}

Smith, Thomas H. ^{[3
]}

Foulds, Gemma A. ^{[1
]}

Bailey, Michael D. ^{[3
]}

Gowen-MacDonald, James ^{[3
]}

Muth, John ^{[8
]}

Schmitz, Marc ^{[9
,10
,11
,12
]}

Cesano, Alessandra ^{[3
]}

Pockley, A. Graham ^{[1
,13
]}

Valk, Peter J. M. ^{[14
]}

Lowenberg, Bob ^{[14
]}

Bornhaeuser, Martin ^{[4
,10
,11
,12
]}

Tasian, Sarah K. ^{[5
,6
,7
]}

Rettig, Michael P. ^{[15
]}

Davidson-Moncada, Jan K. ^{[8
]}

DiPersio, John F. ^{[15
]}

Rutella, Sergio ^{[1
,13
]}

机构：

[1] Nottingham Trent Univ, John van Geest Canc Res Ctr, Nottingham NG11 8NS, England

[2] Princess Margaret Canc Ctr, Div Med Oncol & Hematol, Toronto, ON M5G 2C1, Canada

[3] NanoString Technol Inc, Seattle, WA 98109 USA

[4] Univ Klinikum Carl Gustav Carus, Dept Med, D-01307 Dresden, Germany

[5] Childrens Hosp Philadelphia, Dept Pediat, Div Oncol, Philadelphia, PA 19104 USA

[6] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA

[7] Univ Penn, Sch Med, Philadelphia, PA 19104 USA

[8] MacroGenics Inc, Rockville, MD 20850 USA

[9] Tech Univ Dresden, Fac Med Carl Gustav Carus, Inst Immunol, D-01307 Dresden, Germany

[10] Natl Ctr Tumor Dis NCT, Partner Site Dresden, D-01307 Dresden, Germany

[11] German Canc Consortium DKTK, Partner Site Dresden, D-69120 Heidelberg, Germany

[12] German Canc Res Ctr, D-69120 Heidelberg, Germany

[13] Nottingham Trent Univ, Ctr Hlth Ageing & Understanding Dis CHAUD, Nottingham NG11 8NS, England

[14] Erasmus MC, Dept Hematol, NL-3000 CA Rotterdam, Netherlands

[15] Washington Univ, Dept Internal Med, Div Oncol, St Louis, MO 63110 USA

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2020年 / 12卷 / 546期

基金：

美国国家卫生研究院;

关键词：

GENE-EXPRESSION; T-CELLS; CHECKPOINT BLOCKADE; INDUCTION THERAPY; CLINICAL-OUTCOMES; SIGNATURE; RADIATION; REVEALS; PROFILE; SCORE;

D O I：

10.1126/scitranslmed.aaz0463

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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)-gamma-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-gamma-dominant AML subtypes.

引用

页数：17

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