中性粒细胞直到最近一直被认为是一种均匀的细胞群体，是在稳态和疾病中具有高度保守功能的终分化细胞。在肝细胞癌（HCC）中，肿瘤相关中性粒细胞（TANs）被认为主要起到促瘤作用，促进HCC发展和进展的各个方面。单细胞技术的最新发展现在为我们提供了对HCC肿瘤微环境中的TANs显示的细胞异质性水平的更深入的了解和赞赏，这与我们能够将其与胃癌、胰腺导管腺癌（PDAC）和非小细胞肺癌（NSCLC）的TAN标志相关联的数据集一致。已经确定了具有经典促瘤标志的TANs，以及准备进行抗瘤功能的中性粒细胞，如果被激活和扩增，可能成为一种潜在的治疗方法。近年来，肝细胞癌中对中性粒细胞的治疗靶向主要集中在损害促瘤中性粒细胞的招募上。现在已经将此与免疫检查点阻断相结合，以激发淋巴细胞介导的抗瘤免疫力，同时干扰中性粒细胞介导的免疫抑制。结果，针对中性粒细胞的治疗现在正在进入肝细胞癌的临床试验。与HCC患者中性粒细胞的药物靶向以及离体重编程相结合的治疗方法还处于早期阶段，对中性粒细胞的异质性有更深入的了解，并试图利用它，可能为改善免疫疗法结果铺平道路。本综述将涵盖我们对HCC中性粒细胞异质性理解的最新进展，以及如何利用中性粒细胞来改善HCC免疫疗法。© 2023 作者

Neutrophils, until recently, have typically been considered a homogeneous population of terminally differentiated cells with highly conserved functions in homeostasis and disease. In hepatocellular carcinoma (HCC), tumour-associated neutrophils (TANs) are predominantly thought to play a pro-tumour role, promoting all aspects of HCC development and progression. Recent developments in single-cell technologies are now providing a greater insight and appreciation for the level of cellular heterogeneity displayed by TANs in the HCC tumour microenvironment, which we have been able to correlate with other TAN signatures in datasets for gastric cancer, pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC). TANs with classical pro-tumour signatures have been identified as well as neutrophils primed for anti-tumour functions that, if activated and expanded, could become a potential therapeutic approach. In recent years, therapeutic targeting of neutrophils in HCC has been typically focused on impairing the recruitment of pro-tumour neutrophils. This has now been coupled with immune checkpoint blockade with the aim to stimulate lymphocyte-mediated anti-tumour immunity whilst impairing neutrophil-mediated immunosuppression. As a result, neutrophil-directed therapies are now entering clinical trials for HCC. Pharmacological targeting along with ex vivo reprogramming of neutrophils in HCC patients is, however, in its infancy and a greater understanding of neutrophil heterogeneity, with a view to exploit it, may pave the way for improved immunotherapy outcomes. This review will cover the recent developments in our understanding of neutrophil heterogeneity in HCC and how neutrophils can be harnessed to improve HCC immunotherapy.© 2023 The Author(s).