Wang Yingxin, Ma Jiakang, Liu Yuhao, Cui Weiheng, Chu Xiaodong, Lin Yusheng, Wang Lu
Institute of Precision Cancer Medicine and Pathology, School of Medicine, and Minister of Education Key Laboratory of Tumor Molecular Biology, and State Key Laboratory of Bioactive Molecules and Druggability Assessment, Jinan University, 601 Huangpu Avenue West, Guangzhou, 510632, Guangdong, China.
Department of General Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Cancer Immunol Immunother. 2025 May 19;74(7):210. doi: 10.1007/s00262-025-04049-5.
Neutrophils are integral to the frontline defense against pathogenic bacterial and fungal invasions. Beyond their traditional roles, these cells are increasingly recognized for their dualistic contributions to the pathology of autoimmune and inflammatory diseases, as well as their complex involvement in cancer progression. Neutrophils interact with different disease states, highlighting their potential as therapeutic targets. Within tumor microenvironment (TME), tumor-associated neutrophils (TANs) exhibit a functional dichotomy, capable of either fostering or impeding tumor growth and metastasis. This binary functional potential of TANs, under certain conditions, suggests a reversible state that could transition from tumor-promoting to tumor-eradicating phenotypes. Despite the critical implications of such functional plasticity, systematic studies of TAN behavioral shifts in the context of cancer immunotherapy remain scarce. Herein, we review recent advancements in the understanding of TANs within the TME, highlighting their binary regulatory effects on solid tumors. Leveraging the latest insights from experimental and clinical research, this review elucidates the complex roles of TANs in tumor development and explores their molecular interactions as potential therapeutic targets. The elucidation of these mechanisms holds promise for novel cancer treatment strategies, aiming to improve patient outcomes by manipulating the tumor-promoting or -suppressing functions of TANs.
中性粒细胞是抵御致病性细菌和真菌入侵的一线防御的重要组成部分。除了其传统作用外，这些细胞对自身免疫性疾病和炎症性疾病病理的双重作用以及它们在癌症进展中的复杂参与越来越受到认可。中性粒细胞与不同的疾病状态相互作用，凸显了它们作为治疗靶点的潜力。在肿瘤微环境（TME）中，肿瘤相关中性粒细胞（TANs）表现出功能二分法，既能促进也能阻碍肿瘤生长和转移。在某些条件下，TANs的这种二元功能潜力表明存在一种可逆状态，可从促肿瘤表型转变为抑肿瘤表型。尽管这种功能可塑性具有关键意义，但在癌症免疫治疗背景下对TAN行为转变的系统研究仍然匮乏。在此，我们综述了对TME中TANs理解的最新进展，强调了它们对实体瘤的二元调节作用。利用实验和临床研究的最新见解，本综述阐明了TANs在肿瘤发展中的复杂作用，并探索了它们作为潜在治疗靶点的分子相互作用。对这些机制的阐明有望为新型癌症治疗策略提供依据，旨在通过操纵TANs的促肿瘤或抑肿瘤功能来改善患者预后。
