TIGIT and PD-1 expression atlas predicts response to adjuvant chemotherapy and PD-L1 blockade in muscle-invasive bladder cancer
TIGIT and PD-1 expression atlas predicts response to adjuvant chemotherapy and PD-L1 blockade in muscle-invasive bladder cancer
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TIGIT 和 PD-1 表达图谱可预测肌层浸润性膀胱癌对辅助化疗和 PD-L1 阻断的反应。
DOI：
10.1038/s41416-022-01703-y
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发表时间：
2022-01-17
影响因子：
8.8
通讯作者：
Wang, Zewei
中科院分区：
文献类型：
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作者：
Liu, Zhaopei;Zeng, Han;Wang, Zewei
背景TIGIT和PD-1是两种检查点受体，可通过独立的途径调节免疫细胞的功能状态。然而，基于TIGIT和PD-1表达的免疫分类的临床意义在肌肉浸润性膀胱癌（MIBC）中仍不清楚。方法将来自四个独立队列的MIBC患者分为三组。通过Kaplan-Meier曲线和考克斯回归模型进行生存分析。免疫组织化学和CIBERSORT算法检测免疫组织化学结构。采用流式细胞术检测25例新鲜肿瘤组织中CD 8（+）T细胞的功能状态。结果I群（TIGIT（low）PD-1（low））免疫浸润性差，FGFR 3突变率高; II群（TIGIT（low）PD-1（high））免疫浸润性强，CD 8 + T细胞增多，预后好; III群（TIGIT（high））免疫微环境抑制性强，CD 8 + T细胞耗竭，基础分子亚型减少。聚类III患者的生存率最差，但可以从辅助化疗和抗PD-L1免疫治疗中获益更多，并且还表现出有限的FGFR 3信号转导特征，但激活了免疫系统和EGFR相关通路。结论基于TIGIT/PD-1的危险分层具有明显的免疫和分子特征，可作为MIBC患者辅助化疗和免疫治疗等系统治疗反应的预测指标。
Background TIGIT and PD-1 are checkpoint receptors that could regulate the functional status of immune cells through independent pathways. However, the clinical significance of immune classification based on TIGIT and PD-1 expression remains unclear in muscle-invasive bladder cancer (MIBC). Methods Patients with MIBC from four independent cohorts were categorised into three clusters. Survival analysis conducted through Kaplan-Meier curves and Cox regression model. Immune contexture was measured by immunohistochemistry and CIBERSORT algorithm. Twenty-five fresh tumour tissue samples were utilised to evaluate functional state of CD8(+) T cells by flow cytometry. Results Cluster I (TIGIT(low)PD-1(low)) contained widely poor immune infiltrates with higher FGFR3 mutation, Cluster II (TIGIT(low)PD-1(high)) exhibited a highly infiltrated contexture with increased cytolytic CD8(+) T cells and had the best prognosis, Cluster III (TIGIT(high)) presented a suppressive tumour microenvironment (TME) featured by exhausted CD8(+) T cells and basal molecular subtype. Patients of Cluster III had the worst survival but could benefit more from adjuvant chemotherapy and anti-PD-L1 immunotherapy, and also presented limited FGFR3 signalling signature but activated immunotherapeutic and EGFR-associated pathway. Conclusions TIGIT/PD-1-based risk stratification with distinct immune and molecular features could be served as a predictor for systematic therapeutic response including adjuvant chemotherapy and immunotherapy in MIBC patients.