Wang Xiao, Zhang Yueqin, Li Anan, Zhou Chuanzan, Xu Sen, Gu Zongting, Wang Wei, Nan Peng, Tao Ran
General Surgery, Cancer Center, Department of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
Urology and Nephrology Center, Department of Urology, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
J Gastroenterol. 2025 Sep 19. doi: 10.1007/s00535-025-02291-3.
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with limited treatment options. Immunotherapy, though effective in various tumors, has limited efficacy in PDAC due to immune tolerance. Thus, identifying new targets to enhance immunotherapy response is crucial.
This study used bioinformatics analysis and public database data to identify STYK1 as a potential PDAC biomarker. We analyzed STYK1 expression in PDAC tissues, its link to patient prognosis and immune cell infiltration. In vitro experiments assessed the impact of STYK1 knockdown on PDAC cell proliferation, migration, and invasion. Immunohistochemical analysis was performed on 79 PDAC tissue samples to evaluate CD8 T cell infiltration. In vivo studies examined the effects of STYK1 knockdown on tumor growth, T cell infiltration and activation, especially with anti-PD-L1 antibodies. We also investigated the molecular mechanisms of STYK1's regulation of T cell infiltration, focusing on its association with CCL20 and its role beyond the PD-1/PD-L1 pathway.
Elevated STYK1 expression in PDAC tissue is associated with poor prognosis and reduced CD8 T cell infiltration. STYK1 knockdown inhibits PDAC cell proliferation, migration, and invasion in vitro. In vivo, it decreases tumor growth and, when combined with anti-PD-L1 antibody treatment, significantly enhances T cell infiltration and activation without affecting PD-L1 expression. STYK1 regulates T cell infiltration via CCL20, independently of the PD-1/PD-L1 signaling pathway.
STYK1 is a potential predictive biomarker for immunotherapy response in PDAC, as its regulation of T cell infiltration via CCL20, independent of the PD-1/PD-L1 pathway, may provide a strategy to potentially augment immunotherapy efficacy, pending mechanistic confirmation.
胰腺导管腺癌（PDAC）是一种致死率很高的恶性肿瘤，治疗选择有限。免疫疗法虽然在多种肿瘤中有效，但由于免疫耐受，在PDAC中的疗效有限。因此，识别新的靶点以增强免疫治疗反应至关重要。
本研究利用生物信息学分析和公共数据库数据，将STYK1鉴定为一种潜在的PDAC生物标志物。我们分析了STYK1在PDAC组织中的表达、其与患者预后和免疫细胞浸润的关联。体外实验评估了敲低STYK1对PDAC细胞增殖、迁移和侵袭的影响。对79例PDAC组织样本进行免疫组织化学分析，以评估CD8 T细胞浸润情况。体内研究考察了敲低STYK1对肿瘤生长、T细胞浸润和激活的影响，特别是与抗PD-L1抗体联合使用时的影响。我们还研究了STYK1调节T细胞浸润的分子机制，重点关注其与CCL20的关联及其在PD-1/PD-L1通路之外的作用。
PDAC组织中STYK1表达升高与预后不良和CD8 T细胞浸润减少相关。敲低STYK1在体外可抑制PDAC细胞的增殖、迁移和侵袭。在体内，它可减少肿瘤生长，并且与抗PD-L1抗体治疗联合使用时，可显著增强T细胞浸润和激活，而不影响PD-L1表达。STYK1通过CCL20调节T细胞浸润，独立于PD-1/PD-L1信号通路。
STYK1是PDAC免疫治疗反应的潜在预测生物标志物，因为其通过CCL20调节T细胞浸润，独立于PD-1/PD-L1通路，这可能为潜在增强免疫治疗疗效提供一种策略，有待机制确认。
