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

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.

The Prognostic Value of CD206 in Solid Malignancies: A Systematic Review and Meta-Analysis

“…In the manuscripts included in this review, multiple authors found a (more) significant result when a ratio of CD206 + -cells over the total amount of CD68 + TAMs was analyzed, over CD206 alone [ 26 , 39 , 40 ]. Moreover, multiple authors stated an inverse correlation between the presence of CD206 and the M1-marker CD86, where CD206 high and CD86 low -expression were associated with a significantly worse survival as compared to that of CD206 low CD86 high [ 41 , 42 , 43 , 44 ]. It can therefore be hypothesized that is not the total amount of TAMs or M2-macrophages that have an impact on the survival, but rather the ratio of anti- (M1) and protumorigenic (M2) macrophages over the total amount of macrophages that could be independent prognosticators for the oncological patient’s survival [ 45 , 46 , 47 ].…”

“… OS (multi) 1.94 1.06–3.55 16 Zhu et al [ 61 ] China Hepatocellular Carcinoma OS 2.37 ¶ 1.06–5.31 90 IHC Abcam clone NA Qual. Cholangiocarcinoma 17 Sun et al [ 41 ] China Intrahepatic cholangiocarcinoma OS 1.55 1.16–2.07 322 IHC Abcam clone NA Quant. PFS 1.42 1.05–1.91 Head and neck cancers 18 Ooft et al [ 14 ] Netherlands Nasopharyngeal carcinoma / NA NA 91 IHC 1C9 Quant.…”

Imaging of Inflammation in Spinal Cord Injury: Novel Insights on the Usage of PFC-Based Contrast Agents

“…Moreover, in M1 cells a slight, but significant, increase in CD206 expression was observed, alone or in combination with CD86. CD206 + /CD86 + cells should represent a mixed M1/M2 cell population that is switching from M1 phenotype (pro-inflammatory) to M2 phenotype (anti-inflammatory) [ 51 , 54 , 55 ]. In M2 cells the expression of CD206 was unaffected ( Figure 3 and Figure S3 ), only showing a significant decrease at 24 h post-incubation, but remaining included in a range of high expression values (from 100% to 83%).…”

A Myeloid Signature-Based Nomogram Predicts the Postoperative Recurrence of Intrahepatic Cholangiocarcinoma

“…Nomograms are statistical models developed to maximize predictive accuracy and this tool has shown its advantages in personalized prognosis in various cancers ( Cheng et al, 2019 ). Yet, most of nomograms established to date for iCCA patients mainly focused on clinicopathologic characteristics ( Jing et al, 2018 ; Liu et al, 2018 ; Zhang et al, 2018 ; Zhang et al, 2019 ; Chen et al, 2020 ; Sun et al, 2020 ; Yu et al, 2020 ). In this study, we built a nomogram based on the MRS, a signature of the myeloid response balance in the tumor immune microenvironment, to provide personalized prognosis for patients with iCCA after resection.…”