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High-resolution analysis of mononuclear phagocytes reveals clinically relevant markers in human colo-rectal liver metastasis

ABSTRACT: Macrophages (Mf) are the most abundant mononuclear phagocytes in tumor tissues and hold promise as therapeutic targets and indicators of disease progression. In this work, we mapped by single-cell analysis the distinct Mf populations infiltrating the invasive margin and normal adjacent regions of human colo-rectal liver metastasis (CLM), and we exploited this information to identify non redundant markers with clinical relevance. Different populations were enriched in the invasive margin, including early-mature, inflammatory Mf (MoMf) expressing the monocytic markers S100A12 and SERPINB2, and a more mature population (TAMs) expressing CD68, GPNMB and TREM2. TAMs were enriched in pathways of matrix degradation, angiogenesis and lipid metabolism, similarly to dysfunctional macrophages described in other tumors. Cell-cell interaction analysis with CD8+ T cells defined opposing roles of MoMf, predicted to interact via IL-15, and TAMs, engaging T cells via IL-20 and IL-10. By multiplex immunofluorescence in CLM sections, we confirmed that SERPINB2 and GPNMB are expressed by different Mf subsets, with distinct topographical distribution and opposite association with patient clinical outcome.

ORGANISM(S): Homo sapiens

PROVIDER: GSE200068 | GEO | 2023/05/02

REPOSITORIES: GEO

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