Cathepsin L as a dual-target to mitigate muscle wasting while enhancing anti-tumor efficacy of anti-PD-L1.

ABSTRACT: Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy; however, their use is frequently associated with immune-related adverse events (irAEs). In this study, anti-PD-L1 therapy exacerbates muscle wasting in tumor-bearing male mice despite its anti-tumor efficacy, accompanied by an accumulation of CD8⁺ T cells in muscle. Single-cell RNA sequencing identifies these cells as tissue-resident memory-like CD49a⁺ CD8⁺ T cells. While CD8⁺ T cell depletion prevents muscle wasting, it compromises the anti-tumor efficacy of anti-PD-L1. To resolve this paradox, we identify cathepsin L (CTSL) as a dual-target capable of suppressing both tumor progression and CD8⁺ T cell-mediated muscle wasting, through integrative transcriptomic an

SUBMITTER: Park SY 

PROVIDER: S-EPMC12663269 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature