Systemic and intratumoral balances between monocytes/macrophages and lymphocytes predict prognosis in hepatocellular carcinoma patients after surgery.

Rui Liao,Ning Jiang,Jian-Ping Gong,Cheng-You Du,Shi-Qiao Luo,Ping Huang,Zhuo-Wei Tang,De-Wei Li

doi:10.18632/oncotarget.9049

Abstract

The peripheral neutrophil-monocyte/lymphocyte ratio (NMLR) and intratumoral CD16/CD8 ratio (iMLR) may have prognostic value in hepatocellular carcinoma (HCC) patients after curative resection. In this study, the circulating NMLR was examined 387 HCC patients who underwent curative resection between 2006 and 2009. Intratumoral levels of CD4, CD8, CD16 and CD68 and the CD16/CD8 ratio were determined immunohistologically. The prognostic values of clinicopathological parameters, including NMLR and iMLR, were evaluated. NMLR was predictive of overall survival (OS) and recurrence-free survival (RFS) when patients in the training cohort (n = 256) were separated into high (> 1.2) and low (≤ 1.2) NMLR subgroups. NMLR was also an independent predictor of low alpha-fetoprotein (AFP) expression and early recurrence. High NMLR was associated with increases in clinicopathological variables, including alanine aminotransferase (ALT), tumor number, tumor size and BCLC stage. In addition, iMLR strongly predicted risk of recurrence and patient survival, and was positively correlated with NMLR. These findings were confirmed in an independent validation patient cohort (n = 131). Peripheral NMLR and iMLR may thus be useful prognostic markers, and anti-inflammatory treatment may be beneficial in HCC patients after curative hepatectomy.

Highlights

Hepatocellular carcinoma (HCC) is a malignant tumor with high incidence worldwide [1]
We developed an integrated indicator derived from peripheral neutrophil, monocyte, and lymphocyte levels to predict the outcomes of HCC after curative resection
Accumulating evidence suggests that cancer cells can upregulate inflammatory processes that subsequently impact patient survival in various cancers [6, 13]

Summary

Introduction

Hepatocellular carcinoma (HCC) is a malignant tumor with high incidence worldwide [1]. It is necessary to identify patients with a high risk of recurrence for increased monitoring and to make appropriate treatment-related decisions. The causes of the high recurrence rate in HCC are complex and multifactorial. Two of the most significant factors affecting recurrence are the tumor-promoting effects of chronic inflammation and the malignant biological behaviors of cancer cells [3, 4]. Most HCC patients have a history of chronic liver disease, mainly induced by hepatitis B or C viral infection. In these patients, the accumulation of inflammatory cells likely contributes to the malignant potential of cancer cells and HCC formation [5]. Some hepatic inflammatory/ immune cells, such as tumor-associated macrophages and cancer-associated fibroblasts, are activated by tumor cells, further enhancing tumor phenotypes, proliferation, angiogenesis, and invasion [6,7,8]

Methods

Results

Conclusion