| Accession |
PRJCA023407 |
| Title |
Bulk and single cell RNA sequence of GP73 Knockout and WT Mice |
| Relevance |
Medical |
| Data types |
Transcriptome or Gene expression
|
| Organisms |
Mus musculus
|
| Description |
Immunotherapy targeting immune checkpoints has achieved revolutionary success, but its application in solid tumors remains limited, largely due to the hypoxic tumor microenvironment. Hypoxia induces metabolic reprogramming in tumor cells, known as the Warburg effect, and also leads to exhaustion of immune cells, thereby assisting in immune escape by tumors. Here, we show GP73, a protein located on the membrane of the Golgi apparatus, which correlates positively with T cell activation. Deletion of GP73 in mouse T cells (GP73fl/fl) results in faster growth of subcutaneous MC38 tumors and promotes lung metastasis of B16-F10 melanoma cells. Single-cell RNA sequencing of tumor-infiltrating immune cells from GP73fl/fl mice reveals a decrease in the proportion of cytotoxic CD8+ T cell subsets and an increase in exhausted CD8+ T cell subsets. Importantly, this exhaustion is not dependent on changes in immune checkpoint molecules but is due to insufficient glycolytic capacity. Further analysis showed that GP73 is essential for regulating the effector function of CD8+ T cells in tumors by influencing glycolysis regulated by HIF-1α in CD8+ T cells. Enhanced expression of HIF-1α in GP73fl/fl mouse T cells restores glycolytic levels. Overexpression of GP73 in T cells enhances the ability of T cells for adoptive immunotherapy. These findings reveal the role of GP73 in regulating T cell glycolysis and may offer new therapeutic strategies for the prognosis and treatment of clinical tumor immunotherapy. |
| Sample scope |
Single cell |
| Release date |
2024-11-07 |
| Biomaterial provider |
Academy of Military Medical Science |
| Grants |
| Agency |
program |
Grant ID |
Grant title |
| National Natural Science Foundation of China (NSFC)
|
|
81972696
|
|
|
|
| Submitter |
Yuan
Cao (labs.net@gmail.com)
|
| Organization |
The 960th Hosptial of PLA |
| Submission date |
2024-02-02 |
