Distinct patterns and prognostic values of tumor-infiltrating macrophages in hepatocellular carcinoma and gastric cancer

Jin-Qing Li, Xing-Juan Yu, Yong-Chun Wang, Li-Yun Huang, Chao-Qun Liu, Limin Zheng, Yu-jing Fang, Jing Xu

Macrophages (Mφs) constitute a major component of the leukocyte infiltrate and perform distinct roles in different tumor microenvironments. This study aimed to characterize the distribution, composition and prognostic value of Mφs in hepatocellular carcinoma (HCC) and gastric cancer (GC). Immunohistochemistry and immunofluorescence were used to identify Mφ subsets in HCC and GC tissues. Kaplan-Meier analysis and Cox regression models were applied to estimate the overall survival (OS) for HCC and GC patients. The results showed that the density of Mφs decreased in the intra-tumor region (IT) of HCC, but remarkably increased in the IT of GC, as compared with their non-tumor regions (NT). In HCC, most CD68(+) Mφs were CD204(+) and CD169(+) cells in the NT region; however, there was a significant decrease in the percentage of CD169(+) Mφ in the IT region. In contrast, CD68(+) Mφs comprised a smaller percentage of CD204(+) than the CD169(+) subpopulation in the NT region, while more CD204(+) but fewer CD169(+) cells were present in the IT region of GC. The density of CD204(+) Mφs correlated with poor prognosis in HCC, and CD169(+) Mφs were associated with good survival in both HCC and GC. Moreover, the combination of low numbers of CD204(+) and high numbers of CD169(+) Mφs was associated with improved OS in both GC and HCC. Mφs display tissue-specific distributions and distinct composition patterns in HCC and GC tissues. Our results suggested that different types of tumors might use diverse strategies to reconstitute Mφ patterns to promote tumor progression.