Neutrophils, the most abundant circulating leukocytes in human, play an indispensable role in the innate immune response to microbial infections. However, the contribution of tumor-associated neutrophils (TANs) to cancer progression and tumor immunity has been a matter of debate for decades. A higher neutrophil-to-lymphocyte ratio is associated with adverse overall survival in many solid tumors. Preclinical evidence exists to support both anti-tumor and pro-tumor activities of TANs, and TANs employ diverse mechanisms to influence tumor progression and metastasis. Here, we focus our review on the immunosuppressive mechanism of TANs and highlight how neutrophils can operate to dampen both innate and adaptive immunity to promote tumorigenesis. Here we discuss the intriguing and sometimes controversial connection between TANs and granulocytic/polymorphonuclear myeloid-derived suppressor cells (G/PMN-MDSCs). The molecular mechanisms underlying neutrophils' role in immunosuppression provide potential therapeutic targets for cancer treatment, either as monotherapies or as a part of combinatorial regimens. Therefore, we also highlight a number of neutrophil-targeting approaches that may improve the efficacy of current anticancer therapies, especially cancer immunotherapy. Currently interest is surging in the understanding and targeting of immunosuppressive neutrophils, with the goal of developing novel therapeutic strategies in the battle against cancer.

中文翻译：

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癌症中免疫抑制性中性粒细胞的合理靶向。

中性粒细胞是人类中最丰富的循环白细胞，在对微生物感染的天然免疫反应中起着不可或缺的作用。然而，数十年来，肿瘤相关的中性粒细胞（TANs）对癌症进展和肿瘤免疫力的贡献一直是争论的问题。在许多实体瘤中，较高的嗜中性粒细胞与淋巴细胞比例与不良的总体生存率相关。临床前证据支持TAN的抗肿瘤和促肿瘤活性，并且TAN采用多种机制来影响肿瘤的进展和转移。在这里，我们将重点放在TANs的免疫抑制机制上，并强调中性粒细胞如何发挥作用来抑制先天和适应性免疫，从而促进肿瘤发生。在这里，我们讨论了TAN与粒细胞/多形核髓系髓样抑制细胞（G / PMN-MDSC）之间的有趣关系，有时甚至是有争议的关系。中性粒细胞在免疫抑制中发挥作用的分子机制为癌症治疗提供了潜在的治疗靶标，无论是作为单一疗法还是作为组合疗法的一部分。因此，我们还着重介绍了许多靶向中性粒细胞的方法，这些方法可能会提高当前抗癌疗法（尤其是癌症免疫疗法）的疗效。当前的兴趣是对免疫抑制中性粒细胞的理解和靶向，其目的是在对抗癌症的过程中开发新的治疗策略。在免疫抑制中的作用可作为单一疗法或作为联合疗法的一部分，为癌症治疗提供潜在的治疗靶点。因此，我们还着重介绍了许多靶向中性粒细胞的方法，这些方法可能会提高当前抗癌疗法（尤其是癌症免疫疗法）的疗效。当前的兴趣是对免疫抑制中性粒细胞的理解和靶向，其目的是开发新的治疗策略来对抗癌症。在免疫抑制中的作用可作为单一疗法或作为联合疗法的一部分，为癌症治疗提供潜在的治疗靶点。因此，我们还着重介绍了许多靶向中性粒细胞的方法，这些方法可能会提高当前抗癌疗法（尤其是癌症免疫疗法）的疗效。当前的兴趣是对免疫抑制中性粒细胞的理解和靶向，其目的是开发新的治疗策略来对抗癌症。