Tumor-Derived CDC37 Inhibits Antigen Cross-Presentation in Dendritic Cells and Impairs Anti-Tumor Immunity in Breast Cancer.

ABSTRACT: Tumor mutational burden (TMB), usually representing high immunogenicity, cannot always predict treatment response of immune checkpoint blockade (ICB). Here, it is showed that defective antigen cross-presentation in type 1 conventional dendritic cells (cDC1) is responsible for lacking tumor-specific cytotoxic T lymphocytes (CTLs) in triple-negative breast cancer (TNBC) patients. Mechanistically, tumor cytosolic CDC37, shuttled via extracellular vesicles (EVs) into the endosomes of intratumor dendritic cells (DCs), inhibits antigen cross-presentation by locking antigen binding to HSP90 and precluding their translocation from endosomes to cytoplasm. CDC37 knockdown in tumor cells or inhibiting CDC37/HSP90 interaction in DCs efficiently promotes antigen translocation and enhances their cross-p

SUBMITTER: Wang R 

PROVIDER: S-EPMC12849997 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature