ArticleNature communications2024
Hsc70 promotes anti-tumor immunity by targeting PD-L1 for lysosomal degradation.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- Targeted PD-L1 degradation with an injectable hydrogel reverses chemotherapy-induced compensatory immunosuppression and enhances antitumor immunity.Materials today. Bio · 2026Article
- Role of CMTM6 in disease pathogenesis and clinical translation potential (Review).Molecular medicine reports · 2026Review
- Reprogramming PD-L1 endosomal recycling and lysosomal degradation via engineered exosome-based nanocomposites overcomes immune resistance in lung cancer brain metastasis.Materials today. Bio · 2026Article
- mCancer science · 2026Article
- The mannosyltransferase DPM1 regulates the activity of ER-stress sensor IRE1 in colorectal cancer.Nature communications · 2026Article
- Mechanisms of TRIM21-mediated RUNX2 degradation via chaperone-mediated autophagy in periodontitis.Cell biology and toxicology · 2026Article
- The application of drug delivery systems based on targeted protein degradation chimeras in disease treatment strategies.Journal of nanobiotechnology · 2026Review
- Ceramide disrupts TM9SF2-PGK1 axis to redirect PD-L1 trafficking and enhance antitumor immunity.Nature communications · 2026Article
- Targeting endosomal trafficking-mediated antigen escape to resensitize myeloma to CAR-T therapy.Journal for immunotherapy of cancer · 2026Article
- Targeting HSP90 in cancer: advances in the development of inhibitors, mechanisms of action, and therapeutic applications.Molecular cancer · 2026Review
- Strategies to target PD-1/PD-L1 in the tumor microenvironment.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Lung Cancer in Never-Smokers: Risk Factors, Driver Mutations, and Therapeutic Advances.Diagnostics (Basel, Switzerland) · 2026Review
- Berberine induces PD-L1 degradation via the autophagy-lysosome pathway through the PI3K-Akt pathway and enhances immunogenic cell death in triple-negative breast cancer.Frontiers in immunology · 2026Article
- Chaperone-mediated autophagy as a regulator of hallmarks of cancer.Frontiers in oncology · 2026Review
- RNASEH2C enhances TRAF3IP1 to degrade RAI14 in lysosomes thus hindering macrophage antigen presentation and advancing liver cancer.Cell death & disease · 2025Article
- Article
- From foe to friend: Rewiring oncogenic pathways through artificial selenoprotein to combat immune-resistant tumor.Journal of pharmaceutical analysis · 2025Article
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- Proteostasis of immune checkpoint receptors.The Biochemical journal · 2025Review
- Targeting ALDH16A1 mediated thioredoxin lysosomal degradation to enhance ferroptosis susceptibility in SMARCA4-deficient NSCLC.Nature communications · 2025Article
Corrections and comments
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Authors and funding
17 authors.
Funding
Abstract
Immune checkpoint inhibition targeting the PD-1/PD-L1 pathway has become a powerful clinical strategy for treating cancer, but its efficacy is complicated by various resistance mechanisms. One of the reasons for the resistance is the internalization and recycling of PD-L1 itself upon antibody binding. The inhibition of lysosome-mediated degradation of PD-L1 is critical for preserving the amount of PD-L1 recycling back to the cell membrane. In this study, we find that Hsc70 promotes PD-L1 degradation through the endosome-lysosome pathway and reduces PD-L1 recycling to the cell membrane. This effect is dependent on Hsc70-PD-L1 binding which inhibits the CMTM6-PD-L1 interaction. We further identify an Hsp90α/β inhibitor, AUY-922, which induces Hsc70 expression and PD-L1 lysosomal degradation. Either Hsc70 overexpression or AUY-922 treatment can reduce PD-L1 expression, inhibit tumor growth and promote anti-tumor immunity in female mice; AUY-922 can further enhance the anti-tumor efficacy of anti-PD-L1 and anti-CTLA4 treatment. Our study elucidates a molecular mechanism of Hsc70-mediated PD-L1 lysosomal degradation and provides a target and therapeutic strategies for tumor immunotherapy.
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