Survival impact of immune cells infiltrating peritumoral area of hepatocellular carcinoma.
Survival impact of immune cells infiltrating peritumoral area of hepatocellular carcinoma.
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据报道，肿瘤微环境中的炎症和免疫细胞与几种癌症的肿瘤进展相关。2004年至2013年期间，共有225例接受初次和根治性肝切除术治疗肝细胞癌（HCC）的患者入组本研究。通过免疫组织化学（IHC）评价肿瘤相关中性粒细胞（TAN）、M2巨噬细胞（TAM;肿瘤相关巨噬细胞）、CD 8 + T细胞和调节性T细胞（TCLs），并评价其与患者临床病理特征和预后的关系。首先针对TAN进行IHC。我们没有发现肿瘤内和肿瘤周围的TAN与临床病理特征之间的关系，除了纤维包膜和肿瘤浸润到包膜。接下来，通过IHC评价TAM、CD 8+细胞和Tcl 4。在瘤周区域，TAN和TAM（r = 0.36，p = 0.001）或TNM（r = 0.16，p = 0.008）显示正相关，而TAN和CD 8+细胞显示负相关（r =-0.16，p = 0.02）。至于生存结局，在瘤周区域，高TAN（p = 0.0398）、低CD 8+细胞（p = 0.0275）和高TAMs（p = 0.001）与较差的总生存期（OS）显着相关。此外，高TAN（p = 0.010）和高TAM（p = 0.00125）与更差的无病生存期（DFS）显著相关。最后，我们通过结合这些细胞的表达模式，建立了一个风险签名模型。与低风险签名组相比，高风险签名组的OS（p = 0.0277）和DFS（p = 0.0219）显著更差。我们基于HCC瘤周区域的免疫细胞的风险特征可以预测根治性肝切除术后HCC患者的预后。在这项研究中，我们发现，HCC肿瘤部位的炎症和免疫细胞浸润与患者的预后显着相关。我们还通过HCC癌旁组织免疫细胞浸润评估了风险信号，它可能成为HCC患者根治性肝切除术后新的预后指标。
Inflammatory and immune cells in the tumor microenvironment are reported to be associated with tumor progression in several cancers. In total, 225 patients who underwent initial and curative hepatectomy for hepatocellular carcinoma (HCC) from 2004 to 2013 were enrolled in this study. Tumor‐associated neutrophils (TANs), M2 macrophages (TAMs; tumor‐associated macrophages), CD8+ T cells, and regulatory T cells (Tregs) were evaluated by immunohistochemistry (IHC), and their relationships with patient clinicopathological characteristics and prognosis were evaluated. IHC was performed focusing on TANs first. We could not find a relationship between intratumoral and peritumoral TANs and clinicopathological features except for the fibrous capsule and infiltration of tumors into capsule. Next, TAMs, CD8+ cells and Tregs were evaluated by IHC. At the peritumoral area, TANs and TAMs (r = 0.36, p = 0.001) or Tregs (r = 0.16, p = 0.008) showed a positive correlation, whereas TANs and CD8+ cells showed a negative correlation (r = −0.16, p = 0.02). As for survival outcomes, at the peritumoral area, high TANs (p = 0.0398), low CD8+ cells (p = 0.0275), and high TAMs (p = 0.001) were significantly associated with worse overall survival (OS). In addition, high TANs (p = 0.010), and high TAMs (p = 0.00125) were significantly associated with worse disease‐free survival (DFS). Finally, we established a risk signature model by combining the expression patterns of these cells. The high‐risk signature group had significantly worse OS (p = 0.0277) and DFS (p = 0.0219) compared with those in the low‐risk signature group. Our risk signature based on immune cells at the peritumoral area of the HCC can predict patient prognosis of HCC after curative hepatectomy. In this study, we showed that infiltration of inflammatory and immune cells at peri‐tumoral site of HCC showed a significant association with patients’ prognosis. We also made risk signature evaluated by the infiltration of immune cells at peri‐tumoral site of HCC, and it might to be a new prognostic marker of patients with HCC after curative hepatectomy.
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