Inhibition of 3-mercaptopyruvate sulfurtransferase enhances CD8
8 affiliations
- 1Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Switzerland
- 2Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Switzerland; Institute of Pharmacology, University of Bern, Switzerland
- 3Institute of Pharmacology, University of Bern, Switzerland
- 4Section of Pharmacology, Department of Oncology, Microbiology and Immunology, University of Fribourg, Switzerland
- 5Theodor Kocher Institute, University of Bern, Switzerland
- 6Biochemistry Department, Faculty of Pharmacy and Biotechnology, German University in Cairo (GUC), Cairo, Egypt
- 7Pharmacology and Toxicology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt; University of London at European Universities in Egypt (EUE), New Administrative Capital, Egypt
- 8Institute of Pharmaceutical Sciences of Western Switzerland, University of Geneva, Switzerland; Institute of Pharmacology, University of Bern, Switzerland; Department of Anaesthesiology, Pharmacology, Intensive Care and Emergency Medicine, University of Geneva, Switzerland; Corresponding author. Institute of Pharmacology, University of Bern, Switzerland.
Abstract
Hydrogen sulfide (H 2 S) is a redox-active gasotransmitter implicated in tumor progression and immune regulation. The enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) is a key contributor to endogenous H 2 S and polysulfide production, but its role in tumor–immune interactions remains poorly defined. Here, we show that 3-MST is the most abundantly expressed H 2 S-synthesizing enzyme in human renal cell carcinoma cells (RCC) and that high 3-MST expression correlates with reduced patient survival. Pharmacological inhibition of 3-MST lowered intracellular H 2 S levels in Renca renal carcinoma cells, suppressed proliferation, induced apoptosis, disrupted cellular metabolism, and increased expression of immune-related genes and proteins. In immune cells, partial inhibition of 3-MST promoted T cell activation, as evidenced by increased CD69 expression on CD3 + , CD4 + , and CD8 + T cells. In contrast, complete inhibition of 3-MST, achieved by high concentrations of the inhibitor, modestly reduced CD8 + T cell proliferation. Functionally, 3-MST inhibition potentiated antigen-specific CD8 + T cell-mediated killing of tumor cells, an effect further amplified by PD-L1 blockade. These results establish 3-MST as a redox-sensitive metabolic driver of tumor growth and immune evasion in RCC and demonstrate that its inhibition can boost antitumor immune responses, offering a potential avenue for combination immunotherapy.
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BibTeX
@article{urwyler2026inhibition,
title = {{Inhibition of 3-mercaptopyruvate sulfurtransferase enhances CD8}},
author = {Muriel Urwyler and Marietta Margareta Korsos and Eloise Dupuychaffray and Nikita Markov and Kelly Ascenção and Maria Petrosino and Karim Zuhra and Darko Stojkov and Sara Barcos and Jérémie Tachet and Pragallabh Purwar and Montserrat Alvarez and Aurélien Pommier and Mohamed Z. Gad and Reham M. Abdel-Kader and Csaba Szabo and Carole Bourquin},
journal = {Redox Biology},
year = {2026},
month = oct,
doi = {10.1016/j.redox.2026.104373},
url = {https://doi.org/10.1016/j.redox.2026.104373},
note = {CC BY},
}
RIS
TY - JOUR
TI - Inhibition of 3-mercaptopyruvate sulfurtransferase enhances CD8
AU - Muriel Urwyler
AU - Marietta Margareta Korsos
AU - Eloise Dupuychaffray
AU - Nikita Markov
AU - Kelly Ascenção
AU - Maria Petrosino
AU - Karim Zuhra
AU - Darko Stojkov
AU - Sara Barcos
AU - Jérémie Tachet
AU - Pragallabh Purwar
AU - Montserrat Alvarez
AU - Aurélien Pommier
AU - Mohamed Z. Gad
AU - Reham M. Abdel-Kader
AU - Csaba Szabo
AU - Carole Bourquin
PY - 2026
DA - 2026/10/30
JO - Redox Biology
DO - 10.1016/j.redox.2026.104373
UR - https://doi.org/10.1016/j.redox.2026.104373
AB - Hydrogen sulfide (H 2 S) is a redox-active gasotransmitter implicated in tumor progression and immune regulation. The enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) is a key contributor to endogenous H 2 S and polysulfide production, but its role in tumor–immune interactions remains poorly defined. Here, we show that 3-MST is the most abundantly expressed H 2 S-synthesizing enzyme in human renal cell carcinoma cells (RCC) and that high 3-MST expression correlates with reduced patient survival. Pharmacological inhibition of 3-MST lowered intracellular H 2 S levels in Renca renal carcinoma cells, suppressed proliferation, induced apoptosis, disrupted cellular metabolism, and increased expression of immune-related genes and proteins. In immune cells, partial inhibition of 3-MST promoted T cell activation, as evidenced by increased CD69 expression on CD3 + , CD4 + , and CD8 + T cells. In contrast, complete inhibition of 3-MST, achieved by high concentrations of the inhibitor, modestly reduced CD8 + T cell proliferation. Functionally, 3-MST inhibition potentiated antigen-specific CD8 + T cell-mediated killing of tumor cells, an effect further amplified by PD-L1 blockade. These results establish 3-MST as a redox-sensitive metabolic driver of tumor growth and immune evasion in RCC and demonstrate that its inhibition can boost antitumor immune responses, offering a potential avenue for combination immunotherapy.
SN - 2213-2317
ER -