Multi-cellular phenotypic dynamics during the progression of an immunocompetent breast cancer model.
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Gsell L, Watson SS, Sutevski I, Massara M, Soukup K, Eroglu A, Mold JE, Cougnoux A, Joyce JA, Hausser J
iScience 28 (11) 113808 [2025-11-21; online 2025-10-23]
The breast tumor microenvironment (TME) has recently been profiled at high resolution by performing single-cell RNA sequencing (scRNAseq) on patient samples. However, from patients' samples, analyzing the temporal dynamics of the TME is ethically, practically and scientifically challenging. Revealing these dynamics could structure inter-tumor heterogeneity into a temporally ordered sequence of causes and consequences in cellular events. Here, we survey the dynamics of the TME by performing scRNAseq at different time points of the progression of a mouse breast tumor allograft model driven by the PyMT antigen. We find that multi-cellular phenotypic dynamics follow one of three possible temporal patterns: stable colonization, wave-like, or progressive increase. In particular, IFN-responsive cancer cells, GzmB+ cytotoxic T cells, as well as C1q macrophages, increase in parallel with tumor progression. These findings establish the single-cell types and phenotypes in a progressing breast tumor, and reveal when these cellular players enter and leave the TME.
PubMed 41280683
DOI 10.1016/j.isci.2025.113808
Crossref 10.1016/j.isci.2025.113808
pmc: PMC12637086
pii: S2589-0042(25)02069-3