Correlation Between Macrophage Polarization And Prognosis Of Hepatocellular Carcinoma

Objective The aim of this study is to determine the prognostic significance of diametrically polarized tumor-associated macrophages (TAMs) in hepatocellular carcinoma (HCC) and their application to risk stratification of patients according to their specific prognostic values.Methods (1) The paraffin blocks of 80 cases of hepatocellular carcinoma confirmed by pathology were collected. (2) The expression of CD68-positive macrophages, CDl lc-positive macrophages and CD206-positive macrophages in macrophages in these tissues was detected by immunohistochemical and immunofluorescence staining, and the relationships with clinicopathologic features and prognosis were evaluated.Results (1) CD68-, CD11- and CD206-positive macrophage staining is mainly seen in the cytoplasm and/or membrane of macrophages. The distribution of CD11c-positive macrophages, CD206-positive macrophages and CD68-positive macrophages in each tumour was forcefully correlated (P<0.001, r=0.462; P< 0.001, r=0.978). The density of CD68-positive macrophages, CD11c-positive macrophages and CD206-positive macrophages was 70.05±25.08 (median,52; range,5-114),23.97±9.04 (median,21; range,3-55) and 53.45 ±21.73 (median,30; range,1-86), respectively. (2) CD68-positive staining was positively correlated with advanced-stage cancer (P= 0.002). CDl lc-positive staining was negatively correlated with the BCLC stage (P= 0.022). CD206-positive staining was positively correlated with age, tumour size, vascular invasion, status of metastasis and TNM stage (P=0.003, P=0.036, P=0.026, P=0.007 and P<0.001, respectively). (3) High versus low CD11c-positive TAM density (P=0.005) and low versus high CD206-positive TAM density (P=0.002) were associated with better overall survival, whereas CD68-positive TAM density had no prognostic significance (low versus high, P=0.065). Furthermore, the presence of these positive staining macrophages did not show any prognostic significance for recurrence-free survival (all P>0.05). Multivariate Cox regression analysis identified CD11c-positive and CD206-positive TAMs as an independent prognostic factor (P<0.001, P=0.031, respectively).Conclusion Intratumoural infiltration of diametrically polarized TAMs, a novel identified independent prognostic factor for survival in patients with HCC, could be combined with the TNM stage and the Barcelona Clinic Liver Cancer stage to improve a risk stratification system.