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

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.

Comparison and validation of the prognostic value of preoperative systemic immune cells in hepatocellular carcinoma after curative hepatectomy

“…Cancer can stimulate platelet activity; conversely, platelets can interact with tumor cells and produce several growth factors that facilitate cancer growth, migration, epithelial–mesenchymal transition, and metastasis . Our recent studies also supported the predictive roles of systemic immune cells (peripheral neutrophil, monocyte, and lymphocyte ratio, neutrophil‐to‐lymphocyte ratio (NLR), monocyte‐to‐lymphocyte ratio (MLR), and neutrophil, monocyte, and lymphocyte ratio (NMLR)) in HCC . Similarly, a number of studies have shown that preoperative peripheral immune cell counts or ratios such as monocyte counts , platelet–lymphocyte ratio (PLR) , and platelet–neutrophil–lymphocyte ratio (PNLR) were potential risk factors for dropout before and for recurrence of patients with HCC after liver resection.…”

“…Although the predictive ability of NMLR was reported previously , here, it was not solely the analysis period change in previous study. For the first time, we developed two specific OS and RFS nomograms for resected HCC prognosis incorporating systemic immune cell counts or ratios based on a comprehensive comparison analysis of their prognostic abilities that could reflect the balance of host inflammatory and immune status.…”

“…The power of prediction of the two nomograms was supported by the C‐index and the calibration curve. These findings might shed light on an important association between the NMLR and ER of HCC, suggesting that the systemic inflammatory response promotes the dissemination of primary HCC tumor cells . Therefore, we believe that our models for estimating individualized outcomes following curative hepatectomy might be of more help to clinicians for thoroughly preparing for potential recurrence if patients maintain an underlying constant systemic inflammatory status.…”

The pretreatment lymphocyte to monocyte ratio predicts clinical outcome for patients with hepatocellular carcinoma: A meta-analysis

“…Subsequently, 3 articles did not meet the inclusion criteria and were therefore excluded. Eventually, seven studies, comprising a total of 2,507 patients, were considered eligible for the present meta-analysis18242526272829. The PRISMA flow diagram of the study selection process was shown in Fig.…”

Metavir and FIB-4 scores are associated with patient prognosis after curative hepatectomy in hepatitis B virus-related hepatocellular carcinoma: a retrospective cohort study at two centers in China

“…Therefore, we compared the relationship between FIB-4 and other inflammation-associated parameters including the Forns index, APRI, Glasgow prognostic score (GPS), prognostic index (PI), and prognostic nutritional index (PNI) [28]. Our results indicated that the FIB-4 score was positively correlated with the Forns index and APRI in both sets (Table S2).…”