Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Nat Commun. 2020 Sep 14;11(1):4611. doi: 10.1038/s41467-020-18244-8.
Pancreatic ductal adenocarcinoma (PDAC) and cancer-associated cachexia (CAC) are multifactorial and characterized by dysregulated inflammatory networks. Whether the proinflammatory cytokine IL-20 is involved in the complex networks of PDAC and CAC remains unclear. Here, we report that elevated IL-20 levels in tumor tissue correlate with poor overall survival in 72 patients with PDAC. In vivo, we establish a transgenic mouse model (KPC) and an orthotopic PDAC model and examine the therapeutic efficacy of an anti-IL-20 monoclonal antibody (7E). Targeting IL-20 not only prolongs survival and attenuates PD-L1 expression in both murine models but also inhibits tumor growth and mitigates M2-like polarization in the orthotopic PDAC model. Combination treatment with 7E and an anti-PD-1 antibody shows better efficacy in inhibiting tumor growth than either treatment alone in the orthotopic PDAC model. Finally, 7E mitigates cachexic symptoms in CAC models. Together, we conclude IL-20 is a critical mediator in PDAC progression.
胰腺导管腺癌（PDAC）和癌症相关恶病质（CAC）是多因素的，并以失调的炎症网络为特征。促炎细胞因子 IL-20 是否参与 PDAC 和 CAC 的复杂网络仍不清楚。在这里，我们报告在 72 名 PDAC 患者的肿瘤组织中升高的 IL-20 水平与总生存率差相关。在体内，我们建立了一种转基因小鼠模型（KPC）和一种原位 PDAC 模型，并检查了抗 IL-20 单克隆抗体（7E）的治疗效果。靶向 IL-20 不仅延长了两种小鼠模型的存活时间并减弱了 PD-L1 的表达，而且还抑制了原位 PDAC 模型中的肿瘤生长并减轻了 M2 样极化。在原位 PDAC 模型中，7E 与抗 PD-1 抗体的联合治疗比单独治疗更能有效地抑制肿瘤生长。最后，7E 减轻 CAC 模型中的恶病质症状。总之，我们得出结论，IL-20 是 PDAC 进展的关键介质。
