Th22细胞通过释放IL-22活化宫颈癌细胞AKT通路促进其增殖

Th22 cells promote cervical cancer progression by releasing IL-22 to activate the AKT pathway

目的研究IL-22及Th22细胞在宫颈癌组织中的表达和频率,分析其与宫颈癌临床分期的相关性,探讨它们与宫颈癌发生发展的关系。方法以西南医院2016年1月至2月收集的32例宫颈癌患者为研究对象,免疫组化、Western blot检测IL-22在宫颈癌组织、癌旁组织和正常宫颈组织中的表达情况;流式细胞技术检测Th22细胞在宫颈癌患者外周血CD4^+T淋巴细胞和肿瘤浸润淋巴细胞中的频率及其表达IL-22情况,探讨其与宫颈癌临床分期的关系;细胞共培养探究IL-22是否通过促进AKT信号通路活化而促进宫颈癌细胞增殖。结果宫颈癌肿瘤组织中IL-22的表达水平显著高于癌旁和正常宫颈组织,而且Ⅲ~Ⅳ期宫颈癌组织IL-22的表达明显高于Ⅰ~Ⅱ期。宫颈癌肿瘤组织浸润淋巴细胞中,Th22细胞频率显著高于宫颈癌患者及正常人的外周血,且与宫颈癌的临床分期正相关。Th22是宫颈癌组织中IL-22主要来源。细胞共培养实验显示IL-22促进了AKT的磷酸化并诱导下游分子的表达。结论 Th22细胞通过释放IL-22活化宫颈癌细胞内AKT通路促使其增殖,干预Th22及其效应分子IL-22是宫颈癌防治的一个潜在靶标。

It has been reported that IL-22 and Th22 lymphocytes play an important role in many tumor types,however whether they play a role in cervical cancer（CC） remains unclear. To investigate the expression and clinicalrelevance of IL-22 and IL-22-producing Th22 cells in CC tissues, IL-22 protein levels in CC tissues weremeasured by Western blot and immunohistochemistry, the frequencies of Th22 cells in tumor tissues and peripheralblood from CC patients and healthy controls were analyzed by flow cytometry, and the association between IL-22 and phosphorylation of AKT were investigated. Data showed that IL-22 protein level was significantly higher in CCtissues than that in peri-tumor tissues and normal cervical tissues. Furthermore, the IL-22 level at Ⅲ-Ⅳ stage ofCC tissues was markedly higher than that at Ⅰ-Ⅱ stage; the Th22 frequency in tumor-filtrating lymphocytes wasmuch higher than those in PBMC of CC patients and normal controls, which correlated with CC clinical staging.Th22 cells were the main cell source of IL-22 in CC tissues. In addition, cell co-culture assay indicated that IL-22 promoted CC cell survival by inducing anti-apoptosis pathway through increasing p-AKT level. Results suggest thatIL-22 and Th22 cells are related to CC cell survival, possible through activating AKT pathway, and thus might bepotential therapeutic targets for patients with CC.