On March 18, the research teams led by Ping-Chih Ho from University of Lausanne, in collaboration with Yingxi Xu & Jianxiang Wang team from Chinese Academy of Medical Sciences and Peking Union Medical College, published a research paper titled "Proteasome-guided haem signalling axis contributes to T cell exhaustion" in Nature.
Depolarized mitochondria accumulate in exhausted CD8⁺ T cells and drive T cell dysfunction, but the underlying mechanism linking mitochondrial state to exhaustion has remained unclear.
Key findings:
Proteasome gene expression in CAR-T cells from patients negatively correlates with therapeutic efficacy, and inhibiting proteasome with bortezomib during CAR-T manufacturing prevents exhaustion and improves anti-tumor function.
This study identifies a mitochondria-proteasome-haem signaling axis that regulates CD8⁺ T cell exhaustion and offers a new strategy to enhance adoptive T cell immunotherapy.
We look forward to further collaborations with SeekGene BioSciences and it is great to see the growing impact of single-cell ATAC + RNA multi-omics in advancing immune research.
