Li Weidong, Huang Xiaodong, Han Xiaowen, Zhang Jiayi, Gao Lei, Chen Hao
Department of Surgical Oncology, Lanzhou University Second Hospital, Lanzhou, China.
Key Laboratory of Environmental Oncology of Gansu Province, Lanzhou University Second Hospital, Lanzhou, China.
Front Immunol. 2024 Nov 29;15:1501293. doi: 10.3389/fimmu.2024.1501293. eCollection 2024.
Cytokines, which are important to the tumor microenvironment (TME), play critical roles in tumor development, metastasis, and immune responses. Interleukin-17(IL-17) has emerged as a key biomarker in many malignancies; however, its precise involvement in gastric cancer is less fully understood. Elevated levels of IL-17 have been observed in stomach diseases such as infection and autoimmune gastritis, indicating that a sustained Th17 response may precede the development of gastric cancer. While IL-17 is related to inflammatory processes that may lead to cancer, its specific influence on gastric cancer development and therapy needs to be completely understood. Specifically, the release of IL-17A by diverse immune cells has been associated with both tumor development and inhibition in gastric cancer. It may impact tumor development through mechanisms such as boosting cell proliferation, inducing angiogenesis, and enabling immune cell recruitment or, conversely, suppressing tumor growth via the activation of anti-tumor immune responses. The dual role of IL-17 in cancer, along with its various effects depending on the TME and immune cell composition, highlights the complexity of its activity. Current research reveals that although IL-17 might serve as a target for immunotherapy, its therapeutic potential is hindered by its various activities. Some studies have shown that anti-IL-17 drugs may be helpful, especially when paired with immune checkpoint inhibitors, whereas others point to concerns about the validity of IL-17 in gastric cancer therapy. The lack of clinical trials and the heterogeneity of human tumors underscore the necessity for individualized treatment approaches. Further studies are needed to identify the specific mechanisms of IL-17 in gastric cancer and to design targeted therapeutics appropriately.
细胞因子对肿瘤微环境（TME）至关重要，在肿瘤发展、转移和免疫反应中发挥关键作用。白细胞介素-17（IL-17）已成为许多恶性肿瘤的关键生物标志物；然而，其在胃癌中的具体作用尚不完全清楚。在感染和自身免疫性胃炎等胃部疾病中已观察到IL-17水平升高，这表明持续的Th17反应可能先于胃癌的发生。虽然IL-17与可能导致癌症的炎症过程有关，但其对胃癌发展和治疗的具体影响仍需全面了解。具体而言，多种免疫细胞释放的IL-17A与胃癌的肿瘤发展和抑制均有关联。它可能通过促进细胞增殖、诱导血管生成和促使免疫细胞募集等机制影响肿瘤发展，或者相反，通过激活抗肿瘤免疫反应来抑制肿瘤生长。IL-17在癌症中的双重作用，以及其取决于TME和免疫细胞组成的各种效应，凸显了其活性的复杂性。目前的研究表明，尽管IL-17可能作为免疫治疗的靶点，但其治疗潜力因其多种活性而受到阻碍。一些研究表明，抗IL-17药物可能有帮助，特别是与免疫检查点抑制剂联合使用时，而另一些研究则对IL-17在胃癌治疗中的有效性表示担忧。缺乏临床试验以及人类肿瘤的异质性强调了个体化治疗方法的必要性。需要进一步研究以确定IL-17在胃癌中的具体机制，并适当设计靶向治疗方法。
