Department of Hematology, Cancer Research Center Groningen, University Medical Center Groningen (UMCG), University of Groningen, Hanzeplein 1/DA13, 9713 GZ Groningen, The Netherlands.
Int J Mol Sci. 2020 Oct 22;21(21):7820. doi: 10.3390/ijms21217820.
The advent of immunotherapy has had a major impact on the outcome and overall survival in many types of cancer. Current immunotherapeutic strategies typically aim to (re)activate anticancer T cell immunity, although the targeting of macrophage-mediated anticancer innate immunity has also emerged in recent years. Neutrophils, although comprising ≈ 60% of all white blood cells in the circulation, are still largely overlooked in this respect. Nevertheless, neutrophils have evident anticancer activity and can induce phagocytosis, trogocytosis, as well as the direct cytotoxic elimination of cancer cells. Furthermore, therapeutic tumor-targeting monoclonal antibodies trigger anticancer immune responses through all innate Fc-receptor expressing cells, including neutrophils. Indeed, the depletion of neutrophils strongly reduced the efficacy of monoclonal antibody treatment and increased tumor progression in various preclinical studies. In addition, the infusion of neutrophils in murine cancer models reduced tumor progression. However, evidence on the anticancer effects of neutrophils is fragmentary and mostly obtained in in vitro assays or murine models with reports on anticancer neutrophil activity in humans lagging behind. In this review, we aim to give an overview of the available knowledge of anticancer activity by neutrophils. Furthermore, we will describe strategies being explored for the therapeutic activation of anticancer neutrophil activity.
免疫疗法的出现对许多类型癌症的预后和总体生存率产生了重大影响。目前的免疫治疗策略通常旨在（重新）激活抗癌 T 细胞免疫，尽管近年来靶向巨噬细胞介导的抗癌先天免疫也已经出现。尽管中性粒细胞在循环中的所有白细胞中约占 60%，但在这方面仍在很大程度上被忽视。然而，中性粒细胞具有明显的抗癌活性，可以诱导吞噬作用、转导作用以及对癌细胞的直接细胞毒性消除。此外，治疗性肿瘤靶向单克隆抗体通过所有表达 Fc 受体的固有细胞触发抗癌免疫反应，包括中性粒细胞。事实上，中性粒细胞的耗竭强烈降低了单克隆抗体治疗的疗效，并在各种临床前研究中增加了肿瘤进展。此外，在鼠类癌症模型中输注中性粒细胞可减少肿瘤进展。然而，有关中性粒细胞抗癌作用的证据是零碎的，主要是在体外检测或鼠类模型中获得的，而在人类中有关抗癌中性粒细胞活性的报道则滞后。在这篇综述中，我们旨在概述中性粒细胞的抗癌活性的现有知识。此外，我们将描述正在探索的用于治疗性激活抗癌中性粒细胞活性的策略。
