| RRC ID |
76710
|
| Author |
Mise-Omata S, Ando M, Srirat T, Nakagawara K, Hayakawa T, Iizuka-Koga M, Nishimasu H, Nureki O, Ito M, Yoshimura A.
|
| Title |
SOCS3 deletion in effector T cells confers an anti-tumorigenic role of IL-6 to the pro-tumorigenic cytokine.
|
| Journal |
Cell Rep
|
| Abstract |
Interleukin (IL)-6 is abundantly expressed in the tumor microenvironment and is associated with poor patient outcomes. Here, we demonstrate that the deletion of the suppressor of cytokine signaling 3 (SOCS3) in T cells potentiates anti-tumor immune responses by conferring the anti-tumorigenic function of IL-6 in mouse and human models. In Socs3-deficient CD8+ T cells, IL-6 upregulates the expression of type I interferon (IFN)-regulated genes and enhances the anti-tumor effector function of T cells, while also modifying mitochondrial fitness to increase mitochondrial membrane potential and reactive oxygen species (ROS) levels and to promote metabolic glycolysis in the energy state. Furthermore, Socs3 deficiency reduces regulatory T cells and increases T helper 1 (Th1) cells. SOCS3 knockdown in human chimeric antigen receptor T (CAR-T) cells exhibits a strong anti-tumor response in humanized mice. Thus, genetic disruption of SOCS3 offers an avenue to improve the therapeutic efficacy of adoptive T cell therapy.
|
| Pages |
112940
|
| Published |
2023-8-8
|
| DOI |
10.1016/j.celrep.2023.112940
|
| PII |
S2211-1247(23)00951-8
|
| PMID |
37582370
|
| IF |
8.109
|
| Resource |
| Mice |
RBRC00144 |
| Human and Animal Cells |
B16 melanoma(RCB1283)
NALM-6(RCB1933)
K562(RCB0027) |
