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
Mice RBRC00144
Human and Animal Cells B16 melanoma(RCB1283) NALM-6(RCB1933) K562(RCB0027)