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Intratumoral IL-17+ Cells and Neutrophils show Strong Prognostic Significance in Intrahepatic Cholangiocarcinoma

  • Hepatobiliary Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Inflammatory reactions at a tumor site have both detrimental and beneficial effects on tumor progression. This study was designed to assess the clinical significance of tumor-infiltrating inflammatory cells in patients with intrahepatic cholangiocarcinoma (ICC).

Methods

A total of 123 consecutive ICC patients who underwent curative resection were enrolled. Tissue microarray and immunohistochemistry were used to analyze the distribution and clinical relevance of IL-17+, FOXP3+, CD8+, CD66b+ cells, and microvessel density (CD34) in different microanatomical areas.

Results

IL-17+ cells, FOXP3+ lymphocytes, CD66b+ neutrophils, and microvessels were enriched predominantly in intratumor (IT) area, whereas CD8+ lymphocytes were most abundant in tumor invasive front. On univariate analyses, increasing IL-17 +IT and neutrophilsIT were significantly associated with worse patient survival. Multivariate analyses revealed that IL-17 +IT (hazard ratio [HR] = 1.59; 95% confidence interval [CI], 1.05–2.41; P = 0.028), neutrophilsIT (HR = 1.76; 95% CI, 1.16–2.65; P = 0.007), and their combination (HR 2.8; 95% CI 1.72–4.57; P < 0.001) were independent prognostic factors, which were superior to conventional clinicopathologic features, such as intrahepatic metastasis and TNM stage. IL-17 +IT significantly correlated with the presence of lymph node metastasis, intrahepatic metastasis, and advanced stages, whereas neutrophilsIT correlated with the presence of vascular invasion. In addition, significant positive correlations were detected among densities of IL-17+ cells, neutrophils, and microvessel density.

Conclusions

Our data suggested that intratumor IL-17+ cells, neutrophils are novel, powerful predictors of prognosis in patients with ICC.

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Acknowledgment

This study was supported by research grants from the State 863 High Technology R&D Project of China (No. 2007AA02Z479), FANEDD (for Q.G.), National Natural Science Foundation of China (No. 30901432, 30972949), Shanghai Rising-Star Program (No. 10QA1401300), and “Chen Guang” project supported by Shanghai Municipal Education Commission and Shanghai Education Development Foundation (No. 11CG02).

Conflict of interest

The authors declare no conflicts of interest.

Author information

Authors and Affiliations

  1. Liver Cancer Institute, Zhongshan Hospital and Shanghai Medical School, Fudan University, Shanghai, People’s Republic of China

    Fang-Ming Gu MD, Qiang Gao MD, Guo-Ming Shi MD, Xin Zhang MD, Jia-Hao Jiang MD, Xiao-Ying Wang MD, Ying-Hong Shi MD, Zhen-Bin Ding MD, Jia Fan MD & Jian Zhou MD

  2. Division of Surgical Oncology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Jiping Wang MD

  3. Institute of Biomedical Sciences, Fudan University, Shanghai, People’s Republic of China

    Jia Fan MD & Jian Zhou MD

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  1. Fang-Ming Gu MD
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  2. Qiang Gao MD
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  4. Xin Zhang MD
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Corresponding author

Correspondence to Jian Zhou MD.

Additional information

F.-M. Gu, Q. Gao, G.-M. Shi, and X. Zhang contributed equally to this study.

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Supplementary material 1 (DOC 70 kb)

10434_2012_2268_MOESM2_ESM.tif

Supplementary Fig. 1 Representative distribution of IL-17, CD66b, FOXP3, CD34, and CD8-positive cells in different microanatomic areas of ICC samples (n = 16). The micrographs at higher magnification show the stained intratumor area (1), invasive edge (2), and noncancerous peritumor area (3). Except that CD8+ cells were mainly enriched in the invasive edge, the remaining types of cells most often were found in the intratumor area. The area between the two dashed lines denotes tumor invasive front (TIFF 7808 kb)

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Gu, FM., Gao, Q., Shi, GM. et al. Intratumoral IL-17+ Cells and Neutrophils show Strong Prognostic Significance in Intrahepatic Cholangiocarcinoma. Ann Surg Oncol 19, 2506–2514 (2012). https://doi.org/10.1245/s10434-012-2268-8

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  • DOI: https://doi.org/10.1245/s10434-012-2268-8

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