Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
Department of Hematologic Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
Int Immunopharmacol. 2021 Sep;98:107890. doi: 10.1016/j.intimp.2021.107890. Epub 2021 Jun 24.
Pancreatic Ductal Adenocarcinoma (PDAC) is characterized by an extensive and dense fibrous stroma, which plays an active role in tumor growth and metastasis. Despite the growing importance of the tumor microenvironment in PDAC prognosis, the immune cell infiltration landscape of PDAC has not been elucidated. In this study, we applied a credible computational algorithm to comprehensively estimate the immune cell infiltration (ICI) patterns of 876 PDAC patients. Two ICI phenotypes were identified, and a ICIscore was constructed using ssGSEA algorithm. The ICIscore could significantly predict the prognosis and chemotherapy benefit of PDAC patients in both the discovery and the five validation cohorts. Multivariate cox analysis also identified the independent predictive role of the ICIscore in PDAC prognosis. A high ICIscore subtype was characterized by immune-active signaling pathways and anti-tumor immunity while a low ICIscore subtype was associated with tumor progressive signaling pathways. Four immunotherapy cohorts further supported the use of the ICIscore as a prognostic biomarker for patients receiving immune checkpoint inhibitors in other cancer types. The ICIscore reveals a close relationship between the ICI environment and prognosis and may provide new treatment strategies for PDAC patients.
胰腺导管腺癌(PDAC)的特征是广泛而密集的纤维基质,它在肿瘤生长和转移中起着积极的作用。尽管肿瘤微环境在 PDAC 预后中的重要性日益增加,但 PDAC 的免疫细胞浸润景观尚未阐明。在这项研究中,我们应用了一种可靠的计算算法来全面评估 876 名 PDAC 患者的免疫细胞浸润(ICI)模式。确定了两种 ICI 表型,并使用 ssGSEA 算法构建了 ICI 评分。ICI 评分可显著预测发现和五个验证队列中 PDAC 患者的预后和化疗获益。多变量 cox 分析还确定了 ICI 评分在 PDAC 预后中的独立预测作用。高 ICI 评分亚型的特点是免疫激活信号通路和抗肿瘤免疫,而低 ICI 评分亚型与肿瘤进展信号通路相关。四个免疫治疗队列进一步支持将 ICI 评分作为接受免疫检查点抑制剂治疗的其他癌症类型患者的预后生物标志物。ICI 评分揭示了 ICI 环境与预后之间的密切关系,可能为 PDAC 患者提供新的治疗策略。