American Association for Cancer Research
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Supplementary Table S4 from Spatial and Temporal Mapping of Breast Cancer Lung Metastases Identify TREM2 Macrophages as Regulators of the Metastatic Boundary

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posted on 2023-12-12, 08:20 authored by Ido Yofe, Tamar Shami, Noam Cohen, Tomer Landsberger, Fadi Sheban, Liat Stoler-Barak, Adam Yalin, Truong San Phan, Baoguo Li, Lea Monteran, Ye'ela Scharff, Amir Giladi, Miriam Elbaz, Eyal David, Anna Gurevich-Shapiro, Chamutal Gur, Ziv Shulman, Neta Erez, Ido Amit

Gene expression enrichment analysis (GSEA)

Funding

U.S. Department of Defense (DOD)

HORIZON EUROPE European Research Council (ERC)

Israel Science Foundation (ISF)

Israel Cancer Research Fund (ICRF)

Worldwide Cancer Research (WCR)

Emerson Collective (Emerson)

History

ARTICLE ABSTRACT

Cancer mortality primarily stems from metastatic recurrence, emphasizing the urgent need for developing effective metastasis-targeted immunotherapies. To better understand the cellular and molecular events shaping metastatic niches, we used a spontaneous breast cancer lung metastasis model to create a single-cell atlas spanning different metastatic stages and regions. We found that premetastatic lungs are infiltrated by inflammatory neutrophils and monocytes, followed by the accumulation of suppressive macrophages with the emergence of metastases. Spatial profiling revealed that metastasis-associated immune cells were present in the metastasis core, with the exception of TREM2+ regulatory macrophages uniquely enriched at the metastatic invasive margin, consistent across both murine models and human patient samples. These regulatory macrophages (Mreg) contribute to the formation of an immune-suppressive niche, cloaking tumor cells from immune surveillance. Our study provides a compendium of immune cell dynamics across metastatic stages and niches, informing the development of metastasis-targeting immunotherapies. Temporal and spatial single-cell analysis of metastasis stages revealed new players in modulating immune surveillance and suppression. Our study highlights distinct populations of TREM2 macrophages as modulators of the microenvironment in metastasis, and as the key immune determinant defining metastatic niches, pointing to myeloid checkpoints to improve therapeutic strategies.This article is featured in Selected Articles from This Issue, p. 2489

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