Dysfunction of exhausted T cells is enforced by MCT11-mediated lactate metabolism
University of Pittsburgh · UPMC Hillman Cancer Center
Abstract
Abstract CD8 + T cells are critical mediators of antitumor immunity but differentiate into a dysfunctional state, known as T cell exhaustion, after persistent T cell receptor stimulation in the tumor microenvironment (TME). Exhausted T (T ex ) cells are characterized by upregulation of coinhibitory molecules and reduced polyfunctionality. T cells in the TME experience an immunosuppressive metabolic environment via reduced levels of nutrients and oxygen and a buildup of lactic acid. Here we show that terminally T ex cells uniquely upregulate Slc16a11 , which encodes monocarboxylate transporter 11 (MCT11). Conditional deletion of MCT11 in T cells reduced lactic acid uptake by T ex cells and improved their…
Citation impact
- FWCI
- 28.97
- Percentile
- 100%
- References
- 54
Authors
17- RMRonal M. PeraltaCorresponding
University of Pittsburgh, UPMC Hillman Cancer Center
- BXBingxian Xie
University of Pittsburgh, UPMC Hillman Cancer Center
- KLKonstantinos Lontos
University of Pittsburgh, UPMC Hillman Cancer Center
- HNHector Nieves-Rosado
University of Pittsburgh, UPMC Hillman Cancer Center
- KSKellie Spahr
University of Pittsburgh, UPMC Hillman Cancer Center
Topics & keywords
- Metabolism
- Cell metabolism
- Chemistry
- Cell biology
- Biochemistry
- Biology
Funding
- CRCancer Research Institute
- NINational Institutes of HealthAwards: P50CA121973, T32CA082084, P50CA097190, DP2AI136598, SU2C-AACR-IRG-04-16, R01AI171483, T32AI089443
- SUStand Up To CancerAward: SU2C-AACR-IRG-04-16
- NCNational Cancer InstituteAwards: P50CA097190, P50CA121973, T32CA082084
- NINational Institute of Allergy and Infectious DiseasesAwards: T32AI089443, T32CA082084, DP2AI136598