ArticleJournal of experimental & clinical cancer research : CR2024
Combined IL6 and CCR2 blockade potentiates antitumor activity of NK cells in HPV-negative head and neck cancer.
Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 14 citations in OpenAlex.
- Construction of a new predictive model in head and neck squamous cell carcinoma based on the investigation of extracellular matrix-associated genes.Oncology letters · 2026Article
- Review
- Targeting cytokine/chemokine signaling to convert immunologically cold tumors into hot: Emerging strategies in cancer immunotherapy.Acta pharmaceutica Sinica. B · 2026Review
- Exercise and CD8Journal of molecular medicine (Berlin, Germany) · 2026Review
- Innovative research on predicting skin flaps necrosis through quantification of the USP4/TNFAIP2 regulated 'M1 macrophages-Tregs axis' via skin barrier monitoring technology.Burns & trauma · 2026Article
- Fusobacterium nucleatum-reprogrammed adipocytes promote tumor cisplatin resistance through the CCL2-CCR2 axis in the necrotic metastatic neck nodes of head and neck carcinoma.Cell communication and signaling : CCS · 2025Article
- Blocking the TCA Cycle in Cancer Cells Potentiates CD36+ T-cell-Mediated Antitumor Immunity by Suppressing ER Stress-Associated THBS2 Signaling.Cancer research · 2025Article
- Igniting Cold Tumors: Multi-Omics-Driven Strategies to Overcome Immune Evasion and Restore Immune Surveillance.Oncology research · 2025Review
- Natural killer cells in skin: a unique opportunity to better characterize the many facets of an overlooked secondary lymphoid organ.Frontiers in immunology · 2025Review
- Unraveling NK cell heterogeneity through single-cell sequencing: insights from physiological and tumor contexts for clinical applications.Frontiers in immunology · 2025Review
- Chemokine ligand 2: beyond chemotaxis-a multifaceted role in tumor progression.Frontiers in immunology · 2025Review
- Inhibition of ATM or ATR in combination with hypo-fractionated radiotherapy leads to a different immunophenotype on transcript and protein level in HNSCC.Frontiers in oncology · 2024Article
- Complement C1q is a key player in tumor-associated macrophage-mediated CD8International journal of biological sciences · 2024Article
- NK cell based immunotherapy against oral squamous cell carcinoma.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundWhile T cell-activating immunotherapies against recurrent head and neck squamous cell carcinoma (HNSCC) have shown impressive results in clinical trials, they are often ineffective in the majority of patients. NK cells are potential targets for immunotherapeutic intervention; however, the setback in monalizumab-based therapy in HNSCC highlights the need for an alternative treatment to enhance their antitumor activity.
methodsSingle-cell RNA sequencing (scRNA-seq) and TCGA HNSCC datasets were used to identify key molecular alterations in NK cells. Representative HPV-positive ( +) and HPV-negative ( -) HNSCC cell lines and orthotopic mouse models were used to validate the bioinformatic findings. Changes in immune cells were examined by flow cytometry and immunofluorescence.
resultsThrough integration of scRNA-seq data with TCGA data, we found that the impact of IL6/IL6R and CCL2/CCR2 signaling pathways on evasion of immune attack by NK cells is more pronounced in the HPV - HNSCC cohort compared to the HPV + HNSCC cohort. In orthotopic mouse models, blocking IL6 with a neutralizing antibody suppressed HPV - but not HPV + tumors, which was accompanied by increased tumor infiltration and proliferation of CD161
conclusionsThese findings demonstrate that dual blockade of IL6 and CCR2 pathways effectively enhances the antitumor activity of NK cells in HPV-negative HNSCC, providing a novel strategy for treating this type of cancer.
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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.