Zhou Yanting, Shen Guobo, Zhou Xikun, Li Jing
State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Chinese Academy of Medical Sciences Research Unit of Oral Carcinogenesis and Management, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Signal Transduct Target Ther. 2025 Jun 4;10(1):178. doi: 10.1038/s41392-025-02242-7.
Neutrophils are the first line of defense in nonspecific immunity (innate immunity) and interact with other immune cells to participate in specific defense mechanisms (adaptive immunity). Studies have shown that the tumor microenvironment (TME) mediates tumor development and recruits neutrophils into tumors to become tumor-associated neutrophils (TANs), an important part of TME, and achieve extended lifespan. TANs can be differentiated into the antitumor or protumor phenotype, and play an important role in tumor occurrence, proliferation and recurrence, invasion and metastasis, angiogenesis, cell necrosis, and so on. Here, we summarize the TAN origin and subtypes found through Single-cell RNA sequencing analysis in different types of tumors in recent literature, and the molecular mechanisms underlying their antitumor and protumor effects on tumors. We focus on the interaction between TANs and immunosuppressive or immunostimulatory TME, as well as signal pathways such as transforming growth factor β (TGF-β) associated with TAN phenotype transition. Based on the summarized mechanisms, we focus on the potential application and latest strategies of TAN-based immunotherapy, chemotherapy, and combination therapy in the preclinical study and clinical trials of tumors. The discussion on promising therapy encompasses five key areas: inhibition of the tumor-promoting effect of TANs, enhancement of the antitumor effect of TANs, targeting the interaction between TANs and the TME, reprogramming of TANs, and drug delivery carriers. Finally, we discuss the potential of TANs and their related markers as emerging biomarkers for predicting the prognosis of cancer patients.
中性粒细胞是非特异性免疫（固有免疫）的第一道防线，并与其他免疫细胞相互作用以参与特异性防御机制（适应性免疫）。研究表明，肿瘤微环境（TME）介导肿瘤发展，并将中性粒细胞募集到肿瘤中，使其成为肿瘤相关中性粒细胞（TANs），这是TME的重要组成部分，并实现延长寿命。TANs可分化为抗肿瘤或促肿瘤表型，并在肿瘤发生、增殖和复发、侵袭和转移、血管生成、细胞坏死等方面发挥重要作用。在这里，我们总结了近期文献中通过单细胞RNA测序分析在不同类型肿瘤中发现的TAN起源和亚型，以及它们对肿瘤的抗肿瘤和促肿瘤作用的分子机制。我们重点关注TANs与免疫抑制或免疫刺激TME之间的相互作用，以及与TAN表型转变相关的信号通路，如转化生长因子β（TGF-β）。基于总结的机制，我们重点关注基于TAN的免疫疗法、化疗和联合疗法在肿瘤临床前研究和临床试验中的潜在应用和最新策略。关于有前景的治疗方法的讨论涵盖五个关键领域：抑制TANs的促肿瘤作用、增强TANs的抗肿瘤作用、靶向TANs与TME之间的相互作用、对TANs进行重编程以及药物递送载体。最后，我们讨论了TANs及其相关标志物作为预测癌症患者预后的新兴生物标志物的潜力。
