STS2 deficiency revives CD8⁺T cells from exhaustion and augments checkpoint blockade efficacy in cancer immunotherapy.

ABSTRACT:

Background

T-cell exhaustion is a major barrier to effective antitumor immunity and limits the efficacy of cancer immunotherapies. This study investigates the role of suppressor of T-cell signaling 2 (STS2, also known as UBASH3A) in regulating CD8⁺ T-cell exhaustion within the tumor microenvironment.

Methods

We used genetic ablation of STS2 in mouse models to assess tumor control and responses to anti-programmed cell death protein 1 (PD-1) checkpoint blockade therapy. CD8⁺ tumor-infiltrating lymphocytes (TILs) were characterized through flow cytometry, mass cytometry, and single-cell transcriptomics. Mechanistic studies included co-immunoprecipitation, protein degradation assays, and endocytosis measurements to elucidate the interplay between STS2 and P

SUBMITTER: Sun F 

PROVIDER: S-EPMC12184412 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature