Figure S1 from The CCR6–CCL20 Axis Promotes Regulatory T-cell Glycolysis and Immunosuppression in Tumors

Pant, Ayush; Jain, Aanchal; Chen, Yiyun; Patel, Kisha; Saleh, Laura; Tzeng, Stephany; Nitta, Ryan T.; Zhao, Liang; Wu, Caren Yu-Ju; Bederson, Maria; Wang, William Lee; Bergsneider, Brandon Hwa-Lin; Choi, John; Medikonda, Ravi; Verma, Rohit; Cho, Kwang Bog; Kim, Lily H.; Kim, Jennifer E.; Yazigi, Eli; Lee, Si Yeon; Rajendran, Sakthi; Rajappa, Prajwal; Mackall, Crystal L.; Li, Gordon; Tyler, Betty; Brem, Henry; Pardoll, Drew M.; Lim, Michael; Jackson, Christopher M.

doi:10.1158/2326-6066.27602237

Figure S1 from The CCR6–CCL20 Axis Promotes Regulatory T-cell Glycolysis and Immunosuppression in Tumors

journal contribution

posted on 2024-11-04, 08:23 authored by Ayush Pant, Aanchal Jain, Yiyun Chen, Kisha Patel, Laura Saleh, Stephany Tzeng, Ryan T. Nitta, Liang Zhao, Caren Yu-Ju Wu, Maria Bederson, William Lee Wang, Brandon Hwa-Lin Bergsneider, John Choi, Ravi Medikonda, Rohit Verma, Kwang Bog Cho, Lily H. Kim, Jennifer E. Kim, Eli Yazigi, Si Yeon Lee, Sakthi Rajendran, Prajwal Rajappa, Crystal L. Mackall, Gordon Li, Betty Tyler, Henry Brem, Drew M. Pardoll, Michael Lim, Christopher M. Jackson

Figure S1: CCR6 and CCL20 expression is increased in multiple tumors.

Funding

National Institute of General Medical Sciences (NIGMS)

United States Department of Health and Human Services

Find out more...

History

ARTICLE ABSTRACT

Regulatory T cells (Treg) are important players in the tumor microenvironment. However, the mechanisms behind their immunosuppressive effects are poorly understood. We found that CCR6–CCL20 activity in tumor-infiltrating Tregs is associated with greater glycolytic activity and ablation of Ccr6 reduced glycolysis and lactic acid production while increasing compensatory glutamine metabolism. Immunosuppressive activity toward CD8+ T cells was abrogated in Ccr6−/− Tregs due to reduction in activation-induced glycolysis. Furthermore, Ccr6−/− mice exhibited improved survival across multiple tumor models compared to wild-type mice and Treg and CD8+ T-cell depletion abrogated the improvement. In addition, Ccr6 ablation further promoted the efficacy of anti-PD-1 therapy in a preclinical glioma model. Follow-up knockdown of Ccl20 with siRNA also demonstrated improvement in antitumor efficacy. Our results unveil CCR6 as a marker and regulator of Treg-induced immunosuppression and identify approaches to target the metabolic determinants of Treg immunosuppressive activity.