Delta-like ligand 4 mediated myeloid-derived suppressor cell metabolic reprogramming promotes neoadjuvant therapy resistance in titin-inactivated triple-negative breast cancer.

ABSTRACT: Triple-negative breast cancer (TNBC) is characterized by complex genomic background and treatment resistance. We first defined "Titin (TTN) inactivation", a state of TTN expression deficiency or mutation, affecting tumor progression. However, how TTN inactivation regulates immune escape and affects therapeutic resistance remains unclear. Using whole-exome sequencing, single-cell transcriptome sequencing, and spatial transcriptome sequencing, we screened the clinical features of TNBC patients with TTN inactivation who accepted neoadjuvant therapy. Meanwhile, we used CRISPR-Cas9 technology to construct various mutant TNBC cell lines. Lentiviral vector carrying TTN and delta-like ligand 4 (DLL4) was validated in vivo to verify potential mechanism. Myeloid-derived suppressor cells (MDSCs) meta

SUBMITTER: Yang Y 

PROVIDER: S-EPMC12669439 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature