CD86+/CD206+ tumor-associated macrophages predict prognosis of patients with intrahepatic cholangiocarcinoma

Dalong Sun; Tiancheng Luo; Pingping Dong; Ningping Zhang; Jing Chen; Shuncai Zhang; Longzi Liu; Ling Dong; Si Zhang

doi:10.7717/peerj.8458

CD86⁺/CD206⁺ tumor-associated macrophages predict prognosis of patients with intrahepatic cholangiocarcinoma

PeerJ. 2020 Jan 22:8:e8458. doi: 10.7717/peerj.8458. eCollection 2020.

Authors

Dalong Sun^#^{1

2

3}, Tiancheng Luo^#^{1

3}, Pingping Dong⁴, Ningping Zhang^{1

3}, Jing Chen⁵, Shuncai Zhang^{1

3}, Longzi Liu⁶, Ling Dong^{1

3}, Si Zhang⁷

Affiliations

¹ Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai, China.
² Department of Gastroenterology and Hepatology, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen, China.
³ Shanghai Institute of Liver Disease, Shanghai, China.
⁴ Department of Surgery, Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
⁵ Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China.
⁶ Department of General Surgery, The First Affliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
⁷ NHC Key Laboratory of Glycoconjugate Research, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai, China.

^# Contributed equally.

Abstract

Background: As 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).

Methods: Immunohistochemical 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.

Results: We 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.

Conclusions: These findings indicate that the CD86⁺/CD206⁺ TAMs model possess potential value as a novel prognostic indicator for ICC patients.

Keywords: CA-199; CD206; CD86; Intrahepatic cholangiocarcinoma; Prognosis; Tumor-associated macrophages.

Grants and funding

This work was supported by the National Natural Science Foundation of China under Grant 81672334, 81573423 and 81770137; Shanghai Science and Technology Commission under Grant 15410710100 and 16ZR1406100; Natural Science Foundation of Jiangxi under Grant 20192BAB215033. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.