Abstract
Simple SummaryHepatocellular carcinoma is the most prevalent primary liver cancer, accounting for >80% of primary liver cancers worldwide. Inflammation has come to light as a hallmark of cancer development, and it has become increasingly apparent over the past decade that tumor-associated inflammation drives the involvement of neutrophils in disease progression and metastasis. Infiltrating TANs exhibit either anti-tumorigenic (N1) or protumorigenic (N2) phenotypes. In the vast majority of solid human tumors, high infiltration with tumor-associated neutrophils (TANs) has been correlated with increased tumor growth, lymph node metastasis, and poor prognosis overall, whereas evidence from other studies advocate that under certain conditions, TANs exert cytotoxic and inhibitory activity towards tumor cells, halting the progression of cancer. In this review, we summarize current evidence on the role of neutrophils in the pathogenesis and progression of HCC and we highlight their potential utilization in HCC prognosis and therapy.Hepatocellular carcinoma represents the most prevalent primary liver cancer worldwide, and it is either caused by intrinsic genetic mutations or by a multitude of extrinsic risk factors. Even though the interplay between chronic inflammatory changes and hepatocarcinogenesis has been at the forefront of clinical investigation for the past few decades, the role of tumor-associated neutrophils (TANs) in HCC development still remains ambiguous. On the one hand, N1 TANs exhibit an anti-tumorigenic activity, mediated by direct or indirect tumor cell lysis, whereas on the other hand, N2 TANs have been correlated with increased HCC growth, invasiveness, and metastasis. The association of an elevated Neutrophil-to-Lymphocyte Ratio (NLR) with poor prognosis in patients with HCC, has been recently brought into spotlight, consolidating its widespread use as a reliable biomarker. Due to the decisive involvement of TANs in HCC pathogenesis and development, the utilization of various neutrophil-centered anticancer treatment modalities has been under clinical experimentation, selectively targeting and modulating the processes of neutrophil recruitment, activation, and migration. This review summarizes current evidence on the role of TANs in HCC pathogenesis and progression, as well as in their potential involvement in tumor therapy, shedding light on emerging anticancer treatment methods targeting neutrophils.
Highlights
Liver cancer was the sixth most commonly diagnosed cancer and the fourth leading cause of cancer death worldwide in 2018, with about 841,000 new cases and 782,000 deaths annually [1,2]
We summarize current evidence on the role of neutrophils in the pathogenesis and progression of HCC and we highlight their potential utilization in HCC prognosis and therapy
A study by He et al showed that granulocyte–macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor (TNF) are significantly expressed in the peritumoral area of HCC, modulating neutrophils to an immunosuppressive profile, enhancing the PD-L1 expression and their capacity to suppress T cells [45]
Summary
Liver cancer was the sixth most commonly diagnosed cancer and the fourth leading cause of cancer death worldwide in 2018, with about 841,000 new cases and 782,000 deaths annually [1,2]. Hepatocellular carcinoma is the most prevalent primary liver cancer, accounting for >80% of primary liver cancers worldwide, with geographical variations among its prevalence, and it is the leading cause of death in patients with cirrhosis, with an annual HCC incidence of 1–6% and patients with decompensated cirrhosis being at a high risk [3]. Chronic inflammation associated with cancer is known to alter the tumor microenvironment, via the infiltration of several immune cell populations into tumors, promoting HCC development [13]. Among others, it has become increasingly apparent over the past decade that neutrophils are implicated in the tumor-associated inflammation that drives disease progression and metastasis [14,15,16]. We summarize current evidence on the role of neutrophils in the pathogenesis and progression of HCC and we highlight their potential utilization in HCC prognosis and therapy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
