Abstract
BackgroundAs the main cellular ingredients of tumor microenvironment, tumor-associated macrophages (TAMs) play a vital role in tumor development and progression. Recent studies have suggested that TAMs are sensitive and specific prognostic factors in numerous cancers. The primary purpose of this study is to determine the prognostic significance of TAMs in intrahepatic cholangiocarcinoma (ICC).MethodsImmunohistochemical staining of CD68, CD86 and CD206 were performed in tissue microarrays containing 322 patients, who underwent surgical resection and were pathologically diagnosed with ICC. The prognostic value of CD68, CD86 and CD206 were evaluated by Kaplan–Meier analysis (log-rank test) and nomogram models.ResultsWe demonstrated that the CD86+/CD206+ TAMs model was an independent prognostic index for ICC patients. Patients with low CD86+ TAMs and high CD206+ TAMs infiltration had a markedly worse prognosis and increased risk of post-operative recurrence when compared to high CD86+ TAMs and low CD206+ TAMs intratumoral infiltration. Furthermore, subgroup analysis indicated that the CD86+/CD206+ TAMs model predicted prognosis of ICC patients more powerfully than single macrophage immunomarker. Interestingly, the CD86+/CD206+ TAMs model could further distinguish prognosis of CA-199 negative ICC patients, who were generally presumed to have a more favorable outcome. In order to further perfect the prognostic value of the CD86+/CD206+ TAMs model, we constructed and validated a postoperative nomogram to predict overall survival and recurrence-free survival time in ICC patients.ConclusionsThese findings indicate that the CD86+/CD206+ TAMs model possess potential value as a novel prognostic indicator for ICC patients.
Highlights
Intrahepatic cholangiocarcinoma (ICC), derived from the intrahepatic biliary tree, ranks second in the morbidity of liver malignancies (Blechacz & Gores, 2008)
Low intratumoral infiltration of CD86+ tumor-associated macrophages (TAMs) positively correlated with higher preoperative carbohydrate antigen 199 (CA-199) (p = 0.014), appearance of lymph node metastasis (p = 0.012), presence of liver cirrhosis (p = 0.008) and advanced TNM staging (p = 0.046); while high CD206+ TAMs infiltration was significantly associated with presence of lymph node metastasis (p = 0.005), vascular invasion (p = 0.038)
While the median recurrence-free survival time (RFS) of Group I, II, III and IV were 58.9, 41.0, 48.5 and 26.7 months (p = 0.002) respectively. These results indicated that integrated analysis of immunomarkers CD86 and CD206 could serve as a more powerful predictor of prognosis in intrahepatic cholangiocarcinoma (ICC) patients
Summary
Intrahepatic cholangiocarcinoma (ICC), derived from the intrahepatic biliary tree, ranks second in the morbidity of liver malignancies (Blechacz & Gores, 2008). Current prognostic models based on integrated clinicopathologic features, such as carbohydrate antigen 199 (CA-199), lymph node metastasis and tumor-node-metastasis (TNM) stage, may not be sufficient in predicting clinical outcomes of ICC patients. A more accurate prognostic model is warranted to be established to better predict clinical outcomes of ICC patients. Subgroup analysis indicated that the CD86+/CD206+ TAMs model predicted prognosis of ICC patients more powerfully than single macrophage immunomarker. The CD86+/CD206+ TAMs model could further distinguish prognosis of CA-199 negative ICC patients, who were generally presumed to have a more favorable outcome. In order to further perfect the prognostic value of the CD86+/CD206+ TAMs model, we constructed and validated a postoperative nomogram to predict overall survival and recurrence-free survival time in ICC patients. Conclusions: These findings indicate that the CD86+/CD206+ TAMs model possess potential value as a novel prognostic indicator for ICC patients
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