Abstract
Tumor-associated macrophages (TAMs), the most abundant infiltrating immune cells in tumor microenvironment, have distinct functions in hepatocellular carcinoma (HCC) progression. CD68+ TAMs represent multiple polarized immune cells mainly containing CD86+ antitumoral M1 macrophages and CD206+ protumoral M2 macrophages. TAMs expression and density were assessed by immunohistochemical staining of CD68, CD86, and CD206 in tissue microarrays from 253 HCC patients. Clinicopathologic features and prognostic value of these markers were evaluated. We found that CD68+ TAMs were not associated with clinicopathologic characteristics and prognosis in HCC. Low presence of CD86+ TAMs and high presence of CD206+ TAMs were markedly correlated with aggressive tumor phenotypes, such as multiple tumor number and advanced tumor-node-metastasis (TNM) stage; and were associated with poor overall survival (OS) (p = 0.027 and p = 0.024, respectively) and increased time to recurrence (TTR) (p = 0.037 and p = 0.031, respectively). In addition, combined analysis of CD86 and CD206 provided a better indicator for OS (p = 0.011) and TTR (p = 0.024) in HCC than individual analysis of CD86 and CD206. Moreover, CD86+/CD206+ TAMs predictive model also had significant prognosis value in α-fetoprotein (AFP)-negative patients (OS: p = 0.002, TTR: p = 0.005). Thus, these results suggest that combined analysis of immune biomarkers CD86 and CD206 could be a promising HCC prognostic biomarker.
Highlights
With an increasing incidence rate, hepatocellular carcinoma (HCC) is ranked the second cause of cancer-related deaths around the world [1]
Multivariate Cox’s regression analysis, after backward stepwise variable selections, suggested that apart from tumor size, tumor differentiation, and vascular invasion, infiltration of CD86+ and CD206+ Tumor-associated macrophages (TAMs) remained as the independent prognostic factors in HCC patients for both overall survival (OS) (HR = 2.178, p = 0.040 and HR = 1.584, p = 0.027) and time to recurrence (TTR) (HR = 1.810, p = 0.006 and HR = 1.872, p = 0.030)
These data suggested that combined analysis of CD86 and CD206 served as a better indicator of survival and recurrence in HCC patients than analyzing individual factors
Summary
With an increasing incidence rate, hepatocellular carcinoma (HCC) is ranked the second cause of cancer-related deaths around the world [1]. Surgical resection is the preferred treatment for HCC. Large cohorts of HCC patients suffer from postoperative recurrence, and have a poor response to systemic chemotherapeutic treatments, with a five-year survival rate of only 30%–40% [2]. Current clinicopathologic factors, such as α-fetoprotein (AFP), tumor-node-metastasis (TNM) stage, and Barcelona clinic liver cancer (BCLC) stage, cannot accurately predict the outcome of HCC patients. Novel prognostic markers need to be developed for more customized HCC treatment. Chronic inflammation provides a favorable surrounding to facilitate HCC progression [3,4]. HCC microenvironment cou2lodf 1b2 e rich resources for identifying novel powerful prognostic biomarkers. ResTuAltMs s predictive model showed strong prognosis value in AFP-negative patients
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