IL-22/IL-22RA1信号轴在胰腺肿瘤干细胞中的功能及机制研究

Cancer stem cells (CSCs) contribute to tumor initiation, progression and therapeutic resistance.The function of CSCs is regulated by surrounding “Niche” cells, a specialized microenvironment. IL-22/IL-22RA1 axis mediates cross-talk between leukocytes and epithelial cells because IL-22 and IL-22RA1 expression are restricted to leukocytes and epithelial cells, respectively. Recently our research reported that this axis paly a critical role in development of pancreatitis, however its role in pancreatic cancer still remain unclear. Based on our pilot study, we found that 1) high expression of IL-22RA1 is associate with poor prognosis of pancreatic cancer patient, 2) IL-22RA1 expression was elevated in pancreatic CSCs, and 3) IL-22 promoted stemness of pancreatic cancer cells. Therefore, we will continue to discover the role and mechanism of IL-22/IL-22RA1 on pancreatic cancer stem cells. Overall our finding may offer a better understanding for IL-22RA1 role during pancreatic cancer progression, a potential biomarker for pancreatic CSCs and target therapy for pancreatic cancer .

肿瘤干细胞与肿瘤的发生发展和耐药性密切相关，其功能受到肿瘤微环境的精密调控。但目前免疫因子对肿瘤干细胞调控的研究还比较少。IL-22由免疫细胞分泌，其受体IL-22RA1只在组织实质细胞中表达，申请人前期成果报道了IL-22/IL-22RA1信号轴在急、慢性胰腺炎病理过程中的重要作用，但其在胰腺肿瘤中的功能尚不明确。我们近期研究发现：1）IL-22RA1高表达与与胰腺癌病人预后呈负相关；2）IL-22RA1在胰腺肿瘤干细胞群中高表达；3）IL-22可以促进胰腺肿瘤细胞的干性。本项目拟在此基础上明确IL-22RA1是否可以作为胰腺肿瘤干细胞的特异性标记物，以及深入解析IL-22/IL-22RA1信号轴在胰腺肿瘤干细胞中的功能及作用机制。该研究将丰富免疫因子及相关信号通路对肿瘤干细胞调控的理论，同时也为胰腺癌新药开发提供了科学依据和理论基础。

肿瘤干细胞与肿瘤的发生发展和耐药性密切相关，其功能受到肿瘤微环境的精密调控。但目前免疫因子对肿瘤干细胞调控的研究还比较少。IL-22由免疫细胞分泌，其受体IL-22RA1只在组织实质细胞中表达，申请人前期成果报道了IL-22/IL-22RA1信号轴在急、慢性胰腺炎病理过程中的重要作用，但其在胰腺肿瘤中的功能尚不明确。申请人研究发现，在胰腺肿瘤中高表达IL-22RA的癌细胞具有一定的干性特征，且可通过与微环境中Th22细胞相互作用以维持其干性和成瘤能力。申请人的研究丰富了免疫微环境对胰腺肿瘤干性的调控理论。此外还提出了通过STAT3抑制剂联合化疗药物靶向这些“干细胞样”胰腺癌细胞的策略。