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

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 sequencin...

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Bibliographic Details
Published in:Cell reports (Cambridge) 2022-05, Vol.39 (8), p.110865-110865, Article 110865
Main Authors: Laviron, Marie, Petit, Maxime, Weber-Delacroix, Eléonore, Combes, Alexis J., Arkal, Arjun Rao, Barthélémy, Sandrine, Courau, Tristan, Hume, David A., Combadière, Christophe, Krummel, Matthew F., Boissonnas, Alexandre
Format: Article
Language:English
Subjects:
Adaptive immunology
breast cancer
Cancer
Immunology
Innate immunity
Life Sciences
Multiphoton imaging
scRNA-seq
spatial distribution
tumor-associated macrophages
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Summary: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. [Display omitted] •TAMs differentiate according to their localization in situ•TAM heterogeneity is associated with resident TAM diversity prior to tumor development•Orthotopic tumor models negate TAM diversity•Similar heterogeneity is found in human breast TAMs The origin of tumor-associated macrophage (TAM) heterogeneity is unclear. Laviron et al. show that TAM diversity is driven by the various tissue territories existing prior to tumor apparition and by the state of tumor malignancy. This provides a definition of TAM heterogeneity according to their spatial distribution in situ.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2022.110865