Coordinated immune networks in leukemia bone marrow microenvironments distinguish response to cellular therapy

Katie Maurer^{1

2

3}, Cameron Y Park^{4

5}, Shouvik Mani^{4

6}, Mehdi Borji^{1

3}, Florian Raths⁷, Kenneth H Gouin 3rd⁷, Livius Penter^{1

2

3

8}, Yinuo Jin^{4

5}, Jia Yi Zhang^{4

5}, Crystal Shin^{4

5}, James R Brenner^{1

2}, Jackson Southard^{1

9}, Sachi Krishna¹⁰, Wesley Lu^{1

9}, Haoxiang Lyu^{1

9}, Domenic Abbondanza^{10

11}, Chanell Mangum¹⁰, Lars Rønn Olsen¹², Michael J Lawson⁷, Martin Fabani⁷, Donna S Neuberg¹³, Pavan Bachireddy¹⁴, Eli N Glezer⁷, Samouil L Farhi¹⁰, Shuqiang Li^{1

9}, Kenneth J Livak^{1

9}, Jerome Ritz^{1

2}, Robert J Soiffer^{1

2}, Catherine J Wu^{1

2

3}, Elham Azizi^{4

5

6}

Affiliations

¹ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
² Harvard Medical School, Boston, MA 02115, USA.
³ Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
⁴ Irving Institute for Cancer Dynamics, Columbia University, New York, NY 10027, USA.
⁵ Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.
⁶ Department of Computer Science, Columbia University, New York, NY 10027, USA.
⁷ Singular Genomics, San Diego, CA 92121, USA.
⁸ Department of Hematology, Oncology, and Tumorimmunology, Campus Virchow Klinikum, Berlin, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 13353 Berlin, Germany.
⁹ Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
¹⁰ Spatial Technology Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
¹¹ Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA.
¹² Department of Health Technology, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.
¹³ Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
¹⁴ Department of Hematopoietic Biology & Malignancy, MD Anderson Cancer Center, Houston, TX 77030, USA.

PMID: 39854478
DOI: 10.1126/sciimmunol.adr0782

Coordinated immune networks in leukemia bone marrow microenvironments distinguish response to cellular therapy

Katie Maurer et al. Sci Immunol. 2025.

. 2025 Jan 24;10(103):eadr0782.

doi: 10.1126/sciimmunol.adr0782. Epub 2025 Jan 24.

Authors

Affiliations

¹ Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
² Harvard Medical School, Boston, MA 02115, USA.
³ Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
⁴ Irving Institute for Cancer Dynamics, Columbia University, New York, NY 10027, USA.
⁵ Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.
⁶ Department of Computer Science, Columbia University, New York, NY 10027, USA.
⁷ Singular Genomics, San Diego, CA 92121, USA.
⁸ Department of Hematology, Oncology, and Tumorimmunology, Campus Virchow Klinikum, Berlin, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, 13353 Berlin, Germany.
⁹ Translational Immunogenomics Laboratory, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
¹⁰ Spatial Technology Platform, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
¹¹ Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA.
¹² Department of Health Technology, Technical University of Denmark, 2800 Kongens Lyngby, Denmark.
¹³ Department of Data Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
¹⁴ Department of Hematopoietic Biology & Malignancy, MD Anderson Cancer Center, Houston, TX 77030, USA.

PMID: 39854478
DOI: 10.1126/sciimmunol.adr0782

Abstract

Understanding how intratumoral immune populations coordinate antitumor responses after therapy can guide treatment prioritization. We systematically analyzed an established immunotherapy, donor lymphocyte infusion (DLI), by assessing 348,905 single-cell transcriptomes from 74 longitudinal bone marrow samples of 25 patients with relapsed leukemia; a subset was evaluated by both protein- and transcriptome-based spatial analysis. In acute myeloid leukemia (AML) DLI responders, we identified clonally expanded ZNF683⁺ CD8⁺ cytotoxic T lymphocytes with in vitro specificity for patient-matched AML. These cells originated primarily from the DLI product and appeared to coordinate antitumor immune responses through interaction with diverse immune cell types within the marrow microenvironment. Nonresponders lacked this cross-talk and had cytotoxic T lymphocytes with elevated TIGIT expression. Our study identifies recipient bone marrow microenvironment differences as a determinant of an effective antileukemia response and opens opportunities to modulate cellular therapy.

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Coordinated immune networks in leukemia bone marrow microenvironments distinguish response to cellular therapy

Affiliations

Coordinated immune networks in leukemia bone marrow microenvironments distinguish response to cellular therapy

Authors

Affiliations

Abstract

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Molecular Biology Databases

Research Materials