Thursday Seminar: Domitille Chalopin-Fillot & Julie Giraud

Presentation entitled “TREM1+ CD163+ myeloid cells are potent immunosuppressive cells and associate with poor survival in human liver cancer”. Resume: “Hepatocellular carcinoma (HCC) is an inflammation-associated cancer arising from viral and non-viral etiologies. Expansion of suppressive myeloid cells is a hallmark of chronic inflammation and cancer, but their heterogeneity in HCC is not fully resolved and might underlie immunotherapy resistance. Here, we present a high resolution atlas of innate immunity cells in HCC and unravel remarkable myeloid cell heterogeneity and myeloid-biased NK cell differentiation. Among three phenotypically distinct subsets of myeloid-derived suppressor cells, we identify a discrete population of TREM1+CD163+ MDSC that expand in the inflamed liver and infiltrate HCC primary tumors. TREM1+CD163+ MDSC most potently suppress T cell activity ex vivo. They highly produce TGFbeta and are spatially enriched at fibrotic lesions in HCC. The density of TREM1+CD163+ MDSC correlate with poor patient survival and resistance to immune checkpoint blockade. Our data support myeloid subset-targeted immunotherapies to treat HCC”.