High-Resolution Analysis of Mononuclear Phagocytes Reveals GPNMB as a Prognostic Marker in Human Colorectal Liver Metastasis

Patients with colorectal liver metastasis (CLM) present with on CLM specimens. In a cohort of patients, a high infiltration of heterogenous clinical outcomes and improved classification is SERPINB2 cells independently associated with longer disease-free needed to ameliorate the therapeutic output. Macrophages (Mf) survival (DFS; P ¼ 0.033), whereas a high density of GPNMB cells hold promise as prognostic classifiers and therapeutic targets. Here, correlated with shorter DFS (P ¼ 0.012) and overall survival (P ¼ stemming from a single-cell analysis of mononuclear phagocytes 0.002). Cell-cell interaction analysis defined opposing roles for infiltrating human CLM, we identified two Mf markers associated MoMf and TAMs, suggesting that SERPINB2 and GPNMB with distinct populations with opposite clinical relevance. The cells are discrete populations of Mf and may be exploited for invasive margin of CLM was enriched in pro-inflammatory mono-further translation to an immune-based stratification tool. This cyte-derived Mf (MoMf) expressing the monocytic marker SER-study provides evidence of how multi-omics approaches can idenPINB2, and a more differentiated population, tumor-associated Mf tify nonredundant, clinically relevant markers for further transla(TAM), expressing glycoprotein nonmetastatic melanoma protein tion to immune-based patient stratification tools and therapeutic B (GPNMB). SERPINB2 MoMf had an early inflammatory profile, targets. GPNMB has been shown to set Mf in an immunosuppreswhereas GPNMB TAMs were enriched in pathways of matrix sive mode. Our high dimensional analyses provide further evidence degradation, angiogenesis, and lipid metabolism and were found that GPNMB is a negative prognostic indicator and a potential closer to the tumor margin, as confirmed by spatial transcriptomics player in the protumor function of Mf populations.