ArticleClinical cancer research : an official journal of the American Association for Cancer Research2024
Targeting Dendritic Cell Dysfunction to Circumvent Anti-PD1 Resistance in Head and Neck Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 11 citations in OpenAlex.
- Dendritic cell diversity and dysfunction in cancer: implications for immunotherapy and therapeutic targeting.Acta pharmacologica Sinica · 2026Review
- Biomarkers Predictive of Immunotherapy Efficacy in Head and Neck Squamous Cell Carcinoma: Current Insights and Future Perspectives.World journal of otorhinolaryngology - head and neck surgery · 2026Review
- Tumor-Induced Splenic Remodeling: Mechanisms of Systemic Immunosuppression and Emerging Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Article
- Cancer-Associated Fibroblast-Targeted Nanomedicine in Solid Tumor Therapy: From Mechanisms of Therapeutic Resistance to Precision Stromal Modulation.International journal of nanomedicine · 2026Review
- Chemokine-chemokine receptor networks in conventional type I dendritic cells: an opportunity to prime and boost anticancer immunity.The Journal of pharmacology and experimental therapeutics · 2025Review
- Targeting Intratumoral Copper Inhibits Tumor Progression via p62-Mediated EZH2 Degradation and Potentiates Anti-PD-1 Immunotherapy in Oral Squamous Cell Carcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The tumor-sentinel lymph node immuno-migratome reveals CCR7⁺ dendritic cells drive response to sequenced immunoradiotherapy.Nature communications · 2025Article
- Unraveling the immunomodulatory role of TIM-3 in head and neck squamous cell carcinoma: implications for targeted therapy.Discover oncology · 2025Review
- Cross-priming in cancer immunology and immunotherapy.Nature reviews. Cancer · 2025Review
- Dendritic cell-based immunotherapy for head and neck squamous cell carcinoma: advances and challenges.Frontiers in immunology · 2025Review
- Dendritic cell effector mechanisms and tumor immune microenvironment infiltration define TLR8 modulation and PD-1 blockade.bioRxiv : the preprint server for biology · 2024Article
- Dendritic cell effector mechanisms and tumor immune microenvironment infiltration define TLR8 modulation and PD-1 blockade.Frontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
purposeNeoadjuvant anti-PD1 (aPD1) therapies are being explored in surgically resectable head and neck squamous cell carcinoma (HNSCC). Encouraging responses have been observed, but further insights into the mechanisms underlying resistance and approaches to improve responses are needed. EXPERIMENTAL
designWe integrated data from syngeneic mouse oral carcinoma (MOC) models and neoadjuvant pembrolizumab HNSCC patient tumor RNA-sequencing data to explore the mechanism of aPD1 resistance. Tumors and tumor-draining lymph nodes (DLN) from MOC models were analyzed for antigen-specific priming. CCL5 expression was enforced in an aPD1-resistant model.
resultsAn aPD1-resistant mouse model showed poor priming in the tumor DLN due to type 1 conventional dendritic cell (cDC1) dysfunction, which correlated with exhausted and poorly responsive antigen-specific T cells. Tumor microenvironment analysis also showed decreased cDC1 in aPD1-resistant tumors compared with sensitive tumors. Following neoadjuvant aPD1 therapy, pathologic responses in patients also positively correlated with baseline transcriptomic cDC1 signatures. In an aPD1-resistant model, intratumoral cDC1 vaccine was sufficient to restore aPD1 response by enhancing T-cell infiltration and increasing antigen-specific responses with improved tumor control. Mechanistically, CCL5 expression significantly correlated with neoadjuvant aPD1 response and enforced expression of CCL5 in an aPD1-resistant model, enhanced cDC1 tumor infiltration, restored antigen-specific responses, and recovered sensitivity to aPD1 treatment.
conclusionsThese data highlight the contribution of tumor-infiltrating cDC1 in HNSCC aPD1 response and approaches to enhance cDC1 infiltration and function that may circumvent aPD1 resistance in patients with HNSCC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.