SENP7 senses oxidative stress to sustain metabolic fitness and antitumor functions of CD8+ T cells.
J Clin Invest
; 132(7)2022 04 01.
Article
in En
| MEDLINE
| ID: mdl-35143421
ABSTRACT
The functional integrity of CD8+ T cells is tightly coupled to metabolic reprogramming, but how oxidative stress directs CD8+ T cell metabolic fitness in the tumor microenvironment (TME) remains elusive. Here, we report that SUMO-specific protease 7 (SENP7) senses oxidative stress to maintain the CD8+ T cell metabolic state and antitumor functions. SENP7-deficient CD8+ T cells exhibited decreased glycolysis and oxidative phosphorylation, resulting in attenuated proliferation in vitro and dampened antitumor functions in vivo. Mechanistically, CD8+ T cell-derived ROS triggered cytosolic SENP7-mediated PTEN deSUMOylation, thereby promoting PTEN degradation and preventing PTEN-dependent metabolic defects. Importantly, lowering T cell-intrinsic ROS restricted SENP7 cytosolic translocation and repressed CD8+ T cell metabolic and functional activity in human colorectal cancer samples. Our findings reveal that SENP7, as an oxidative stress sensor, sustains CD8+ T cell metabolic fitness and effector functions and unveil an oxidative stress-sensing machinery in tumor-infiltrating CD8+ T cells.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
CD8-Positive T-Lymphocytes
/
Neoplasms
Limits:
Humans
Language:
En
Journal:
J Clin Invest
Year:
2022
Document type:
Article
Affiliation country:
China