Wu Songsong, Cao Zhumin, Lu Rongying, Zhang Zhenwang, Sethi Gautam, You Yulai
Department of Radiation Oncology, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Interventional and Vascular Surgery, The Seventh People's Hospital of Chongqing, Chongqing, China.
Cytokine Growth Factor Rev. 2025 Jan 10. doi: 10.1016/j.cytogfr.2025.01.001.
Interleukin-6 (IL-6) is a pro-inflammatory cytokine playing a pivotal role during inflammation and immune responses. In the recent years, the function of IL-6 in the tumor microenvironment (TME) for affecting tumorigenesis and immunotherapy response has been investigated. The genetic mutations are mainly responsible for the development of cancer, while interactions in TME are also important, involving both cancers and non-cancerous cells. IL-6 plays a significant role in these interactions, enhancing the proliferation, survival and metastasis of tumor cells through inflammatory pathways, highlighting its carcinogenic function. Multiple immune cells including macrophages, T cells, myeloid-derived suppressor cells, dendritic cells and natural killer cells can be affected by IL-6 to develop immunosuppressive TME. IL-6 can also participate in the immune evasion through increasing levels of PD-L1, compromising the efficacy of therapeutics. Notably, IL-6 exerts a double-edge sword function and it can dually increase or decrease cancer immunotherapy, providing a challenge for targeting this cytokine in cancer therapy. Highlighting the complicated function of IL-6 in TME can lead to the development of effective therapeutics for cancer immunity.
白细胞介素-6（IL-6）是一种促炎细胞因子，在炎症和免疫反应中起关键作用。近年来，人们对IL-6在肿瘤微环境（TME）中影响肿瘤发生和免疫治疗反应的功能进行了研究。基因突变是癌症发生的主要原因，而TME中的相互作用也很重要，涉及癌细胞和非癌细胞。IL-6在这些相互作用中起重要作用，通过炎症途径增强肿瘤细胞的增殖、存活和转移，突出了其致癌功能。包括巨噬细胞、T细胞、髓源性抑制细胞、树突状细胞和自然杀伤细胞在内的多种免疫细胞可受IL-6影响，从而形成免疫抑制性TME。IL-6还可通过提高PD-L1水平参与免疫逃逸，损害治疗效果。值得注意的是，IL-6发挥着双刃剑的作用，它可以使癌症免疫治疗效果双重增加或降低，这给在癌症治疗中靶向这种细胞因子带来了挑战。突出IL-6在TME中的复杂功能有助于开发有效的癌症免疫治疗方法。
