Immune landscapes predict chemotherapy resistance and immunotherapy response in acute myeloid leukemia.
Jayakumar VadakekolathuMark D MindenTressa HoodSarah E ChurchStephen ReederHeidi AltmannAmy H SullivanElena J VibochTasleema PatelNarmin IbrahimovaSarah E WarrenAndrea ArrudaYan LiangThomas H SmithGemma Ann FouldsMichael D BaileyJames Gowen-MacDonaldJohn MuthMarc SchmitzAlessandra CesanoAlan Graham PockleyPeter J M ValkBob LöwenbergMartin BornhäuserSarah K TasianMichael P RettigJan K Davidson-MoncadaJohn F DipersioSergio RutellaPublished in: Science translational medicine (2021)
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.
Keyphrases
- acute myeloid leukemia
- allogeneic hematopoietic stem cell transplantation
- gene expression
- bone marrow
- high resolution
- end stage renal disease
- dna methylation
- dendritic cells
- immune response
- mesenchymal stem cells
- radiation therapy
- ejection fraction
- squamous cell carcinoma
- young adults
- acute lymphoblastic leukemia
- locally advanced
- diffuse large b cell lymphoma
- peritoneal dialysis
- genome wide
- binding protein
- transcription factor
- hodgkin lymphoma
- tandem mass spectrometry