Xu Huazhen, Chen Xiaojun, Lu Yuqing, Sun Nihao, Weisgerber Karis E, Xu Manzhu, Bai Ren-Yuan
Kennedy Krieger Institute, 707 N Broadway, Lab 520, Baltimore, MD 21205, USA.
Department of Neurosurgery, Johns Hopkins University School of Medicine, 707 N Broadway, Lab 520, Baltimore, MD 21205, USA.
Cancers (Basel). 2025 Aug 7;17(15):2593. doi: 10.3390/cancers17152593.
Neutrophils are increasingly recognized as key players in the tumor microenvironment (TME), displaying functional plasticity that enables them to either promote or inhibit cancer progression. Depending on environmental cues, tumor-associated neutrophils (TANs) may polarize toward antitumor "N1" or protumor "N2" phenotypes, exerting diverse effects on tumor growth, metastasis, immune modulation, and treatment response. While previous studies have focused on the pathological roles of TANs in cancer, less attention has been given to how cancer therapies themselves influence the behavior of TANs. This review provides a comprehensive synthesis of current knowledge regarding the dynamics of TANs in response to major cancer treatment modalities, including chemotherapy, radiotherapy, cell-based immunotherapies, and oncolytic viral and bacterial therapies. We discuss how these therapies influence TAN recruitment, polarization, and effector functions within the TME, and highlight key molecular regulators involved. By consolidating mechanistic and translational insights, this review emphasizes the potential to therapeutically reprogram TANs to enhance treatment efficacy. A deeper understanding of context-dependent TAN roles will be essential for developing more effective, neutrophil-informed cancer therapies.
中性粒细胞越来越被认为是肿瘤微环境(TME)中的关键角色,它们表现出功能可塑性,使其能够促进或抑制癌症进展。根据环境线索,肿瘤相关中性粒细胞(TANs)可能会向抗肿瘤的“N1”或促肿瘤的“N2”表型极化,对肿瘤生长、转移、免疫调节和治疗反应产生不同影响。虽然先前的研究集中在TANs在癌症中的病理作用,但对于癌症治疗本身如何影响TANs的行为关注较少。本综述全面综合了关于TANs对主要癌症治疗方式(包括化疗、放疗、基于细胞的免疫疗法以及溶瘤病毒和细菌疗法)反应动态的当前知识。我们讨论了这些疗法如何影响TME内TANs的募集、极化和效应功能,并强调了涉及的关键分子调节因子。通过整合机制和转化见解,本综述强调了通过治疗性重编程TANs来提高治疗效果的潜力。深入了解依赖于背景的TANs作用对于开发更有效、基于中性粒细胞的癌症治疗至关重要。