4.8 Article

SENP7 senses oxidative stress to sustain metabolic fitness and antitumor functions of CD8+T cells

Journal

JOURNAL OF CLINICAL INVESTIGATION
Volume 132, Issue 7, Pages -

Publisher

AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI155224

Keywords

-

Funding

  1. National Natural Science Foundation of China [31922025, 32170908, 81930040]
  2. National Key Research and Development Program of China [2020YFA0803603]
  3. Shanghai Science and Technology Commission [20JC1410100]

Ask authors/readers for more resources

Research finds that SENP7 can sense oxidative stress, maintain the metabolic state and antitumor functions of CD8+ T cells, with deficient SENP7 cells showing impaired metabolic activity. ROS derived from CD8+ T cells trigger SENP7-mediated PTEN deSUMOylation, promoting PTEN degradation to prevent metabolic defects.
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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available