Identification of CircRNA signature associated with tumor immune infiltration to predict therapeutic efficacy of immunotherapy

Yu Dong, Qian Gao, Yong Chen, Zhao Zhang, Yanhua Du, Yuan Liu, Guangxiong Zhang, Shengli Li, Gaoyang Wang, Xiang Chen (), Hong Liu (), Leng Han () and Youqiong Ye ()
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Yu Dong: Furong Laboratory
Qian Gao: Furong Laboratory
Yong Chen: Fudan University Shanghai Cancer Center
Zhao Zhang: McGovern Medical School at The University of Texas Health Science Center at Houston
Yanhua Du: Shanghai Jiao Tong University School of Medicine
Yuan Liu: McGovern Medical School at The University of Texas Health Science Center at Houston
Guangxiong Zhang: Lin Gang Laboratory
Shengli Li: Shanghai Jiao Tong University School of Medicine (SJTU-SM)
Gaoyang Wang: Shanghai Jiao Tong University School of Medicine
Xiang Chen: Furong Laboratory
Hong Liu: Furong Laboratory
Leng Han: McGovern Medical School at The University of Texas Health Science Center at Houston
Youqiong Ye: Shanghai Jiao Tong University School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: Abstract Circular RNAs (circRNAs) play important roles in the regulation of cancer. However, the clinical implications and regulatory networks of circRNAs in cancer patients receiving immune checkpoint blockades (ICB) have not been fully elucidated. Here, we characterize circRNA expression profiles in two independent cohorts of 157 ICB-treated advanced melanoma patients and reveal overall overexpression of circRNAs in ICB non-responders in both pre-treatment and early during therapy. Then, we construct circRNA-miRNA-mRNA regulatory networks to reveal circRNA-related signaling pathways in the context of ICB treatment. Further, we construct an ICB-related circRNA signature (ICBcircSig) score model based on progression-free survival-related circRNAs to predict immunotherapy efficacy. Mechanistically, the overexpression of ICBcircSig circTMTC3 and circFAM117B could increase PD-L1 expression via the miR-142-5p/PD-L1 axis, thus reducing T cell activity and leading to immune escape. Overall, our study characterizes circRNA profiles and regulatory networks in ICB-treated patients, and highlights the clinical utility of circRNAs as predictive biomarkers of immunotherapy.

Date: 2023
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DOI: 10.1038/s41467-023-38232-y

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