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  • Review Article
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The rewired immune microenvironment in leukemia

Nature Immunology volume 26, pages 351–365 (2025)Cite this article

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Abstract

Leukemias are a class of human cancers that originate from hematopoietic progenitors and are characterized by extensive remodeling of the immune microenvironment. Leukemic cells, on transformation, acquire the ability to evade immune recognition but, despite undergoing genetic and epigenetic changes, retain their characteristic immature immune signature. For this and other reasons, leukemias are often refractory to immune therapies. In the present Review, we cover these areas as a means of improving outcomes from a deeper understanding of immune rewiring, inflammatory signaling and the barriers to successful implementation of immune therapies.

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Fig. 1: Hematopoiesis and malignant transformation lead to distinct types of acute leukemia.
Fig. 2: Remodeling of the BM microenvironment.
Fig. 3: Mechanisms of immunotherapy resistance in human leukemia.

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Acknowledgements

We thank J. C. Balandrán and P. E. Rovatti for critical reading of the manuscript and all the members of the Aifantis laboratory for helpful discussions. I.A. is supported by the National Cancer Institute, the National Institutes of Health, the Vogelstein Foundation, the EvansMDS Foundation, the Department of Defense (grant no. BM210043), the MPN Research Foundation and St. Baldricks Foundation. V.P. was supported by an EMBO postdoctoral fellowship (grant no. EMBO ALTF-742-2020).

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  1. These authors contributed equally: Zoe Ciantra, Varvara Paraskevopoulou.

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  1. Department of Pathology, New York University Grossman School of Medicine, New York, NY, USA

    Zoe Ciantra, Varvara Paraskevopoulou & Iannis Aifantis

  2. Laura & Isaac Perlmutter Cancer Center, New York University Grossman School of Medicine, New York, NY, USA

    Zoe Ciantra, Varvara Paraskevopoulou & Iannis Aifantis

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Ciantra, Z., Paraskevopoulou, V. & Aifantis, I. The rewired immune microenvironment in leukemia. Nat Immunol 26, 351–365 (2025). https://doi.org/10.1038/s41590-025-02096-9

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