Macrophage-targeted immunocytokine leverages myeloid, T, and NK cell synergy for cancer immunotherapy.

Michelle von Locquenghien¹, Pascale Zwicky¹, Ken Xie¹, Diego Adhemar Jaitin¹, Fadi Sheban¹, Adam Yalin², Florian Uhlitz², Chamutal Gur³, Reut Sharet Eshed¹, Eyal David¹, Kfir Mazuz¹, Caroline Jennings Marin², Ankita Sankar², Devin Mediratta², Roberto Avellino¹, Assaf Weiner⁴, Ido Amit⁵

¹Department of Systems Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel.

²Immunai, New York, NY 10016, USA.

³Department of Systems Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel; Rheumatology Department, Hadassah Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 91120, Israel.

⁴Department of Systems Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel; Immunai, Ramat Gan 5252213, Israel.

⁵Department of Systems Immunology, Weizmann Institute of Science, Rehovot 7610001, Israel. Electronic address: ido.amit@weizmann.ac.il.

PubMed DOI

Abstract

Tumor-associated macrophages (TAMs) expressing the myeloid checkpoint TREM2 are key immunosuppressive cells in the tumor microenvironment (TME), driving tumor progression and contributing to poor prognosis in cancer patients. Due to their pivotal role, TAMs have emerged as a promising target for immunotherapies. However, current TAM-targeting monotherapies show limited efficacy, highlighting the n…

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Mentioned Companies

Immunai
affiliation

MeSH Terms

Killer Cells, Natural*Animals0Immunotherapy*Humans0Mice0Tumor Microenvironment0Neoplasms*T-Lymphocytes*Tumor-Associated Macrophages*Macrophages*Mice, Inbred C57BL0Cytokines*Cell Line, Tumor0Myeloid Cells*Interleukin-20Female0Receptors, Immunologic0

Keywords

T and NK cell synergyTME-conditional IL-2TREM2cancer immunotherapycytokinesmyeloid checkpointsmyeloid-targeted immunocytokinesingle-cell genomicssynthetic immunologytumor-associated macrophagestumor-microenvironment modulation

Article Info

PMID: 41265436
DOI: 10.1016/j.cell.2025.10.030
Received: April 2, 2025
Accepted: October 28, 2025

How to Cite

von Locquenghien M et al. Macrophage-targeted immunocytokine leverages myeloid, T, and NK cell synergy for cancer immunotherapy. Cell2025;188(25):7099-7117.e26. doi:10.1016/j.cell.2025.10.030

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