Table 2.
Summary of studies evaluating the role of TANs in HCC prognosis.
| Study (year) | Study Subjects | Primary Outcome | Secondary Outcome |
|---|---|---|---|
| He et al. [45] (2015) | Human/Animal | High NLR is negatively correlated with the OS of patients with HCC | The ratio of PD-L1+ neutrophils-to-PD-1+ T cells is higher in peritumoral tissue and better predicts the DFS of patients with HCC |
| Zhou et al. [54] (2012) | Human/Animal | CXCL5 overexpression alone, or combined with the presence of intratumoral neutrophils, is an independent prognostic indicator for OS and cumulative recurrence | CXCL5 promotes HCC cell proliferation, invasion, and intratumoral neutrophil infiltration via the activation of the PI3K-Akt and ERK1/2 signaling pathways |
| Li et al. [55] (2011) | Human | Increased intratumoral neutrophils are significantly associated with decreased RFS/OS and are identified as an independent prognostic factor of patients with HCC | Intratumoral CD66b+ neutrophils significantly correlated with CD8+ T cells, TGF-β expression, BCLC stage and early recurrence of HCC, whereas peritumoral neutrophils were not associated with the outcome of HCC |
| Zhou et al. [56] (2016) | Human/Animal | The number of CCL2+ or CCL17+ TANs correlates with tumor size, microvascular invasion, tumor encapsulation, tumor differentiation, and stage | Patients whose tumors have lower levels of CCL2+ or CCL17+ cells have longer survival times than those with higher numbers of these cells. |
| Kuang et al. [58] (2011) | Human | Accumulation of neutrophils in peritumoral stroma fosters disease progression via MMP-9 and predicts reduced survival in HCC patients | Accumulation of peritumoral stromal neutrophils coincides with increased VEGF expression and angiogenesis progression at the invading tumor edge of HCC |
| Wang et al. [59] (2019) | Human | Both IDO expression and intratumoral neutrophils infiltration were independent prognostic factors for OS after resection | High IDO expression is a risk factor for intratumoral neutrophils infiltration in HCC patients |
| Terashima et al. [71] (2015) | Human | The objective response rate to HAIC of advanced HCC patients with low NLR is significantly better than that of patients with high NLR | Median PFS and median OS in patients with high NLR is significantly shorter than that of the patients with low NLR |
| Kim et al. [72] (2021) | Human | Elevated NLR explicitly predicts the occurrence of HPD as well as inferior survival rate after PD-1 blockade | HPD is associated with worse PFS and OS as well as deprivation of chances for subsequent treatments |
| Xiao et al. [73] (2014) | Human | High NLR is associated with poor OS and DFS in HCC initially treated by liver transplantation and surgical resection and significantly correlates with the presence of vascular invasion tumor multifocality and higher incidence of AFP ≥ 400 ng/mL | High NLR is associated with poor OS in HCC treated by radiofrequency-ablation, TACE and mixed treatment consisting of locoregional, systemic treatments or supportive care |
| Xu et al. [74] (2018) | Human | Elevated pretransplant NLR has a close association with the OS, RFS and DFS of patients undergoing LT for HCC | Elevated NLR is associated with the presence of vascular invasion and Milan criteria |
| Yang et al. [76] (2020) | Human/Animal | NET formation is enhanced in neutrophils from patients with HCC, especially metastatic HCC | NETs enhance metastatic potential of the trapped HCC cells through activating TLR4/9 |
TAN: tumor-associated neutrophil; HCC: hepatocellular carcinoma; MMP-9: matrix metallopeptidase-9; VEGF: vascular endothelial growth factor; RFS: recurrence-free survival; OS: overall survival; DFS: disease-free survival; NLR: neutrophil-to-lymphocyte ratio; AFP: alpha-fetoprotein; HAIC: hepatic arterial infusion chemotherapy; CCL: C-C motif chemokine ligand; LT: liver transplantation; IDO: indoleamine 2,3-dioxygenase; HPD: hyperprogressive disease; PD-1: Programmed death-1; NET: neutrophil extracellular trap; TLR: toll-like receptor; CXCL: C-X-C motif chemokine ligand; TGF-β: transforming growth factor-β; BCLC: Barcelona Clinic Liver Cancer; VEGF: vascular endothelial growth factor; TACE: transarterial chemoembolization; ERK: extracellular signal-regulated kinase; PI3K: phosphoinositide 3-kinase; Akt: protein kinase B.