Identification of CircRNA signature associated with tumor immune infiltration to predict therapeutic efficacy of immunotherapy.
Yu DongQian GaoYong ChenZhao ZhangYanhua DuYuan LiuGuangxiong ZhangShengli LiGaoyang WangXiang ChenHong LiuLeng HanYouqiong YePublished in: Nature communications (2023)
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.
Keyphrases
- end stage renal disease
- newly diagnosed
- transcription factor
- ejection fraction
- papillary thyroid
- chronic kidney disease
- free survival
- cell proliferation
- stem cells
- prognostic factors
- squamous cell
- signaling pathway
- genome wide
- gene expression
- young adults
- single cell
- bone marrow
- combination therapy
- childhood cancer
- pi k akt
- drug induced