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Updated: Jan 11, 2026

Tractable In Vivo Reprogramming of Tumor Cells to Type 1 Conventional Dendritic Cell-like Cells
Published on: August 1, 2025
Tumor-Derived CDC37 Inhibits Antigen Cross-Presentation in Dendritic Cells and Impairs Anti-Tumor Immunity in Breast
Ruxin Wang1,2, Yunyi Zhang1,2, Xiangyu Meng1,2
1Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China.
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-presentation, which improves ICB therapeutic responses. Clinically, high tumor CDC37 expression is associated with low infiltration of antigen-specific CTLs and poor ICB efficacy in TNBC patients. Therefore, tumor EV-shuttled CDC37 locks antigen/chaperone interaction and impairs antigen cross-presentation in DCs. Moreover, targeting CDC37 is promising to enhance anti-tumor immunity and reverse ICB resistance.
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