The temporal progression of immune remodeling during metastasis.

Longitudinal scRNA-seq reveals distinct stages of immune remodeling before, during, and after metastatic colonization in the lungs of PyMT mice.TLR-NFκB inflammation correlates with pre-metastatic niche formation and involves both tissue-resident and bone marrow-derived myeloid cell populations. Inflammatory lung myeloid cells mirror 'activated' primary tumor MDSCs, suggesting that primary tumor-derived cues induce expression and TLR-NFκB inflammation in the lung. Lymphocytes contribute to the inflammatory and immunosuppressive lung metastatic microenvironment, highlighted by enrichment of cytotoxic NK cells in the lung over time. Cell-cell signaling network modeling predicts cell type-specific regulation and IGF1-IGF1R signaling between neutrophils and interstitial macrophages.