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Supplementary Table 5 from Memory/Active T-Cell Activation Is Associated with Immunotherapeutic Response in Fumarate Hydratase–Deficient Renal Cell Carcinoma

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posted on 2024-06-03, 07:22 authored by Junru Chen, Xu Hu, Junjie Zhao, Xiaoxue Yin, Linmao Zheng, Jingjing Guo, Jianhui Chen, Yongquan Wang, Xinan Sheng, Haiying Dong, Xiaodong Liu, Xingming Zhang, Jiayu Liang, Haolin Liu, Jin Yao, Jiyan Liu, Yali Shen, Zhibin Chen, Zhengyu He, Yaodong Wang, Ni Chen, Ling Nie, Mengni Zhang, Xiuyi Pan, Yuntian Chen, Haoyang Liu, Yaowen Zhang, Yanfeng Tang, Sha Zhu, Jinge Zhao, Jindong Dai, Zilin Wang, Yuhao Zeng, Zhipeng Wang, Haojie Huang, Zhenhua Liu, Pengfei Shen, Hao Zeng, Guangxi Sun

Supplementary Table 5. Multivariate analysis of progression-free survival in patients treated with first-line ICI+TKI.

Funding

1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University

Sichuan Province Science and Technology Support Program (Science and Technology Project of Sichuan)

National Natural Science Foundation of China (NSFC)

Postdoctoral Research Foundation of China (China Postdoctoral Research Foundation)

Natural Science Foundation of Sichuan Province (四川省自然科学基金)

Research Foundation for the Postdoctoral Program of Sichuan University

Post-Doctor Research Project, West China Hospital, Sichuan University

History

ARTICLE ABSTRACT

Fumarate hydratase–deficient renal cell carcinoma (FH-deficient RCC) is a rare and lethal subtype of kidney cancer. However, the optimal treatments and molecular correlates of benefits for FH-deficient RCC are currently lacking. A total of 91 patients with FH-deficient RCC from 15 medical centers between 2009 and 2022 were enrolled in this study. Genomic and bulk RNA-sequencing (RNA-seq) were performed on 88 and 45 untreated FH-deficient RCCs, respectively. Single-cell RNA-seq was performed to identify biomarkers for treatment response. Main outcomes included disease-free survival (DFS) for localized patients, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) for patients with metastasis. In the localized setting, we found that a cell-cycle progression signature enabled to predict disease progression. In the metastatic setting, first-line immune checkpoint inhibitor plus tyrosine kinase inhibitor (ICI+TKI) combination therapy showed satisfactory safety and was associated with a higher ORR (43.2% vs. 5.6%), apparently superior PFS (median PFS, 17.3 vs. 9.6 months, P = 0.016) and OS (median OS, not reached vs. 25.7 months, P = 0.005) over TKI monotherapy. Bulk and single-cell RNA-seq data revealed an enrichment of memory and effect T cells in responders to ICI plus TKI combination therapy. Furthermore, we identified a signature of memory and effect T cells that was associated with the effectiveness of ICI plus TKI combination therapy. ICI plus TKI combination therapy may represent a promising treatment option for metastatic FH-deficient RCC. A memory/active T-cell–derived signature is associated with the efficacy of ICI+TKI but necessitates further validation.