Delineation of an immunosuppressive gradient in hepatocellular carcinoma using high-dimensional proteomic and transcriptomic analyses

Abstract

SignificanceThe roles of tumor-infiltrating leukocytes in mediating cancer progression are well recognized, but a multidimensional analysis of the entire cancer immune system is lacking. Here, we dissected the cancer-immune landscape in hepatocellular carcinoma (HCC) across tumor, nontumor, and peripheral blood cells using time-of-flight mass cytometry, multiplex immunofluorescence tissue staining, and NanoString analysis. We identified various immune subsets that were enriched in the tumor microenvironment and their potential impact on the tumor immunity based on their detailed phenotypes. This study has validated the concept of a cancer-immune gradient and demonstrated in primary HCC that immune-cell subsets become progressively suppressive as they traverse the nontumor to tumor microenvironment. These data have opened avenues for the design of immunotherapeutics in HCC.