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Treatment with Exogenously Added Catalase Alters CD8 T Cell Memory Differentiation and Function
Halil-Ibrahim Aksoylar1,2, Nikolaos Patsoukis1,2
1Division of Hematology-Oncology Beth Israel Deaconess Medical Center Harvard Medical School, Boston, MA, 02215, USA.
Advanced Biology
|April 28, 2022
Summary
Supplementing catalase (CAT) reduces harmful extracellular hydrogen peroxide (H2O2) in the tumor microenvironment. This improves T cell function, activation, and memory differentiation for better cancer immunotherapy outcomes.
Area of Science:
- Immunology
- Cell Biology
- Cancer Therapy
Background:
- Cell-based immunotherapy shows promise for cancer treatment but is hindered by the tumor microenvironment (TME).
- Metabolic reprogramming is crucial for enhancing T cell function, longevity, and persistence within the TME.
- Reactive oxygen species (ROS), including hydrogen peroxide (H2O2), are key mediators of immune cell function but can be detrimental in excess.
Purpose of the Study:
- To investigate the impact of scavenging extracellular H2O2 using catalase (CAT) on T cell redox state, activation, and memory differentiation.
- To evaluate CAT supplementation's effect on T cell fitness and phenotype under chronic and acute activation conditions within the TME context.
Main Methods:
- Supplementation with catalase (CAT) to scavenge extracellular hydrogen peroxide (H2O2).
- In vitro assessment of T cell activation, redox state, and memory differentiation markers under chronic and acute activation.
- Analysis of T cell phenotypes, including exhaustion markers, activation markers, memory markers, and bioenergetic capacity.
Main Results:
- Extracellular H2O2 scavenging by CAT decreased intracellular ROS, enhanced T cell activation, and altered memory differentiation.
- Under chronic activation, CAT treatment promoted CD8 T cells with less exhaustion, increased activation/memory markers, and higher bioenergetic capacity.
- Under acute activation, CAT treatment prevented the transition from stem cell memory/naive (T_SCM/T_N) to central memory (T_CM) phenotypes, enhancing activation and polyfunctionality.
Conclusions:
- Extracellular H2O2 plays a critical role in T cell fitness and memory differentiation.
- Catalase supplementation represents a potential strategy to improve T cell-based cancer immunotherapy by modulating the TME.
- Targeting H2O2 metabolism offers a novel approach to enhance T cell function and therapeutic efficacy in cancer.
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