Expression of CD38 on Macrophages Predicts Improved Prognosis in Hepatocellular Carcinoma

Abstract

<b>Background:</b> CD38 is involved in the adenosine pathway, which represents one of the immunosuppressive mechanisms in cancer. CD38 is broadly expressed across immune cell subsets, including human macrophages differentiated <i>in vitro</i> from monocytes, but expression by tissue-resident macrophages remains to be demonstrated. <b>Methods:</b> Tissue samples were obtained from 66 patients with hepatocellular carcinoma (HCC) from Singapore and analyzed using immunohistochemistry. Tumor-infiltrating leukocytes (TILs) were further examined using DEPArray™, and the phenotype of freshly isolated TILs was determined using flow cytometry. <b>Results:</b> CD38 was frequently co-expressed with the macrophage-specific marker CD68. CD38⁺CD68⁺ macrophage density was associated with improved prognosis after surgery, while total CD68⁺ macrophage density was associated with poor prognosis. DEPArray™ analysis revealed the presence of large (>10 μm), irregularly shaped CD45⁺CD14⁺ cells that resembled macrophages, with concurrent CD38⁺ expression. Flow cytometry also revealed that majority of CD14⁺HLA-DR⁺ cells expressed CD38. <b>Conclusion:</b> CD38 expression was clearly demonstrated on human macrophages in an <i>in vivo</i> setting. The positive association identified between CD38⁺ macrophage density and prognosis may have implications for routine diagnostic work.