尽管中性粒细胞具有细胞毒性，但癌细胞常常利用它们来促进免疫抑制、肿瘤生长和转移。因此，这些细胞在作为潜在的癌症免疫治疗药物方面受到很少的关注。在这里，我们展示了在小鼠模型中，中性粒细胞可以被利用来诱导肿瘤的扫荡和减少转移种植，通过肿瘤坏死因子、CD40激动剂和肿瘤结合抗体的联合作用。相同的组合在体外激活人类中性粒细胞，使它们能够溶解人类肿瘤细胞。机制上，这种治疗使中性粒细胞迅速动员和浸润肿瘤，同时在肿瘤中激活互补作用。互补组分C5a激活中性粒细胞产生白三烯B4，通过黄嘌呤氧化酶刺激活性氧自由基产生，导致氧化损伤和多种肿瘤类型的T细胞独立清除。这些数据将中性粒细胞确定为强大的抗肿瘤免疫介质，并定义了一条炎症途径，可以加以利用以驱动中性粒细胞介导的癌症消灭。 版权所有© 2023 Elsevier Inc.。保留所有权利。

Despite their cytotoxic capacity, neutrophils are often co-opted by cancers to promote immunosuppression, tumor growth, and metastasis. Consequently, these cells have received little attention as potential cancer immunotherapeutic agents. Here, we demonstrate in mouse models that neutrophils can be harnessed to induce eradication of tumors and reduce metastatic seeding through the combined actions of tumor necrosis factor, CD40 agonist, and tumor-binding antibody. The same combination activates human neutrophils in vitro, enabling their lysis of human tumor cells. Mechanistically, this therapy induces rapid mobilization and tumor infiltration of neutrophils along with complement activation in tumors. Complement component C5a activates neutrophils to produce leukotriene B4, which stimulates reactive oxygen species production via xanthine oxidase, resulting in oxidative damage and T cell-independent clearance of multiple tumor types. These data establish neutrophils as potent anti-tumor immune mediators and define an inflammatory pathway that can be harnessed to drive neutrophil-mediated eradication of cancer.Copyright © 2023 Elsevier Inc. All rights reserved.