Spatial and Temporal Mapping of Breast Cancer Lung Metastases Identify TREM2 Macrophages as Regulators of the Metastatic Boundary

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

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish
Pages (from-to)2610-2631
Number of pages22
JournalCancer Discovery
Volume13
Issue number12
DOIs
StatePublished - 12 Dec 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023 American Association for Cancer Research.

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