Proteolysis-targeting chimera against BCL-X_L destroys tumor-infiltrating regulatory T cells.

ABSTRACT: Regulatory T cells (Tregs) play an important role in maintaining immune homeostasis and, within tumors, their upregulation is common and promotes an immunosuppressive microenvironment. Therapeutic strategies that can eliminate Tregs in the tumor (i.e., therapies that do not run the risk of affecting normal tissues), are urgently needed for the development of cancer immunotherapies. Here we report our discovery of B-cell lymphoma extra-large (BCL-X_L) as a potential molecular target of tumor-infiltrating (TI) Tregs. We show that pharmacological degradation of BCL-X_L using a newly developed platelet-sparing BCL-X_L Proteolysis-targeting chimera (PROTAC) induces the apoptosis of TI-Tregs and the activation of TI-CD8⁺ T cells. Moreover, these activitie

SUBMITTER: Kolb R 

PROVIDER: S-EPMC7904819 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature