Tumor-associated macrophage heterogeneity is driven by tissue territories in breast cancer

Marie Laviron; Maxime Petit; Eléonore Weber-Delacroix; Alexis J Combes; Arjun Rao Arkal; Sandrine Barthélémy; Tristan Courau; David A Hume; Christophe Combadière; Matthew F Krummel; Alexandre Boissonnas

doi:10.1016/j.celrep.2022.110865

Tumor-associated macrophage heterogeneity is driven by tissue territories in breast cancer

Cell Rep. 2022 May 24;39(8):110865. doi: 10.1016/j.celrep.2022.110865.

Affiliations

¹ Sorbonne Université, INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, 75013 Paris, France.
² Department of Pathology, ImmunoX Initiative, UCSF Immunoprofiler Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; UCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
³ Department of Pathology, ImmunoX Initiative, UCSF Immunoprofiler Initiative, University of California, San Francisco, San Francisco, CA 94143, USA; UCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA.
⁴ Mater Research Institute-University of Queensland, Translational Research Institute, Brisbane, QLD 4101, Australia.
⁵ Department of Pathology, ImmunoX Initiative, UCSF Immunoprofiler Initiative, University of California, San Francisco, San Francisco, CA 94143, USA.
⁶ Sorbonne Université, INSERM, CNRS, Centre d'Immunologie et des Maladies Infectieuses, Cimi-Paris, 75013 Paris, France. Electronic address: alexandre.boissonnas@upmc.fr.

PMID: 35613577
DOI: 10.1016/j.celrep.2022.110865

Abstract

Tissue-resident macrophages adapt to local signals within tissues to acquire specific functions. Neoplasia transforms the tissue, raising the question as to how the environmental perturbations contribute to tumor-associated macrophage (TAM) identity and functions. Combining single-cell RNA sequencing (scRNA-seq) with spatial localization of distinct TAM subsets by imaging, we discover that TAM transcriptomic programs follow two main differentiation paths according to their localization in the stroma or in the neoplastic epithelium of the mammary duct. Furthermore, this diversity is exclusively detected in a spontaneous tumor model and tracks the different tissue territories as well as the type of tumor lesion. These TAM subsets harbor distinct capacity to activate CD8+ T cells and phagocyte tumor cells, supporting that specific tumor regions, rather than defined activation states, are the major drivers of TAM plasticity and heterogeneity. The distinctions created here provide a framework to design cancer treatment targeting specific TAM niches.

Keywords: CP: Cancer; CP: Immunology; Multiphoton imaging; breast cancer; scRNA-seq; spatial distribution; tumor-associated macrophages.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Breast Neoplasms* / genetics
Breast Neoplasms* / pathology
Female
Humans
Macrophages / pathology
Transcriptome / genetics
Tumor-Associated Macrophages*