Paper Info
Title
Investigation of CRS-associated cytokines in CAR-T therapy with meta-GNN and pathway crosstalk
Abstract
Chimeric antigen receptor T-cell (CAR-T) therapy is a new and efficient cellular immunotherapy. The therapy shows significant efficacy, but also has serious side effects, collectively known as cytokine release syndrome (CRS). At present, some CRS-related cytokines and their roles in CAR-T therapy have been confirmed by experimental studies. However, the mechanism of CRS remains to be fully understood. Based on big data for human protein interactions and meta-learning graph neural network, we employed known CRS-related cytokines to comprehensively investigate the CRS associated cytokines in CAR-T therapy through protein interactions. Subsequently, the clinical data for 119 patients who received CAR-T therapy were examined to validate our prediction results. Finally, we systematically explored the roles of the predicted cytokines in CRS occurrence by protein interaction network analysis, functional enrichment analysis, and pathway crosstalk analysis. We identified some novel cytokines that would play important roles in biological process of CRS, and investigated the biological mechanism of CRS from the perspective of functional analysis. 128 cytokines and related molecules had been found to be closely related to CRS in CAR-T therapy, where several important ones such as IL6, IFN-γ, TNF-α, ICAM-1, VCAM-1 and VEGFA were highlighted, which can be the key factors to predict CRS.
Year
DOI
Venue
2022
10.1186/s12859-022-04917-2
BMC Bioinformatics
Keywords
DocType
Volume
CAR-T therapy, Cytokine release syndrome, Meta-learning graph neural network, Functional enrichment analysis, Pathway crosstalk
Journal
23
Issue
ISSN
Citations 
1
1471-2105
0
PageRank 
References 
Authors
0.34
1
9
Name
Order
Citations
PageRank
Zhenyu Wei100.34
Qi Cheng200.34
Nan Xu300.34
Chengkui Zhao400.34
Jiayu Xu500.34
Liqing Kang600.34
Xiaoyan Lou700.34
Lei Yu831.42
Weixing Feng9114.60