Metabolism of primary colorectal tumor facilitate MDSC infiltration in pre-metastatic liver

Through an integrated transcriptome analysis of orthotopic colorectal cancer tumor-bearing mice and sham-operation mice, we showed the distinct immune microenvironment of pre-metastatic liver and identified MDSCs as the dominated cell type mediating pre-metastatic niche formation. MDSCs instead of other immune cell types were highly infiltrated in the pre-metastatic liver when compared with normal liver. Notably, immunosuppressive factors released by MDSCs such as HIF1a, iNOS, TGFß were significantly up-regulated in the pre-metastatic liver. Increasing immune checkpoint molecules expression also reflected an immunosuppressive condition of pre-metastatic liver. The primary tumor may induce MDSCs accumulation via metabolic mechanism including glycolysis/gluconeogenesis, HIF-1 signaling pathway, and CCL28 chemokine axis. This study depicts the immune cell landscape of pre-metastatic cancer and primary CRC tumor, and provides insights into how MDSCs reshape the pre-metastatic niche facilitating circulating cancer cells colonization. Overall design: Integrated transcriptomic analysis of orthotopic colorectal cancer tumor-bearing mice and sham-operation mice to identify immune landscape of pre-metastatic liver in comparison with normal liver. The corresponding metabolism and signaling pathways that potentially mediates pre-metastatic niche formation are explored.