Gene expression profile of tumor-associated macrophages in human colorectal liver metastasis (CLM)

The immune landscape impacts outcome and therapeutic response in many tumor types, including colorectal liver metastases (CLM). It has long been known that in vitro polarized macrophages differ in morphology. Here we tested the hypothesis that morphology of tumor-associated macrophages (TAMs) in CLM represents a correlate of function with prognostic significance. Density and morphological metrics (area and perimeter) of TAMs were measured and correlated with clinic-pathological prognostic variables. While density of TAMs did not correlate with survival of CLM patients, cell area identified small and large macrophages that associated with 5-year disease-free survival rate of 27.8% and 0.2% respectively (P<0.001). RNA sequencing of morphologically distinct macrophages identified LXR/RXR as the most enriched pathway in large macrophages and upregulation of genes involved in cholesterol metabolism, phagocytosis and downregulation of the inflammatory program. These results support that accurate, morphometric characterization can serve as a simple readout of TAM diversity with prognostic significance. Overall design: RNA-sequencing of small and large tumor associated macrophages in a cohort of 5 patients