ArticleEuropean journal of immunology2016
HLA class I downregulation is associated with enhanced NK-cell killing of melanoma cells with acquired drug resistance to BRAF inhibitors.
Article in European journal of immunology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 36 citations in OpenAlex.
- B7-H6/NKp30 Axis in Melanoma: Translational Rationale, Evidence Gaps, and Therapeutic Considerations.Biomolecules · 2026Review
- Photodynamic therapy with zinc phthalocyanine suppresses immune checkpoints in human melanoma cells.Lasers in medical science · 2026Article
- Article
- Comprehensive characterization of NK cell-related genes in cutaneous melanoma identified a novel prognostic signature for predicting the prognosis, immunotherapy, and chemotherapy efficacy.Discover oncology · 2025Article
- Tumor hypoxia shapes natural killer cell anticancer activities.Journal of molecular medicine (Berlin, Germany) · 2025Review
- Proteasome inhibition enhances the anti-leukemic efficacy of chimeric antigen receptor (CAR) expressing NK cells against acute myeloid leukemia.Journal of hematology & oncology · 2024Article
- Review
- Article
- Enhanced development of functional human NK cells in NOD-scid-IL2rgFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Human Leukocyte Antigen Class I Antigen-Processing Machinery Upregulation by Anticancer Therapies in the Era of Checkpoint Inhibitors: A Review.JAMA oncology · 2022Review
- The Immunogenetics of Melanoma.Advances in experimental medicine and biology · 2022Article
- Co-delivery of gemcitabine and cisplatin via Poly (L-glutamic acid)-g-methoxy poly (ethylene glycol) micelle to improve the in vivo stability and antitumor effect.Pharmaceutical research · 2021Article
- Memory-like Differentiation Enhances NK Cell Responses to Melanoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Article
- Natural Killer Cells and Anti-Cancer Therapies: Reciprocal Effects on Immune Function and Therapeutic Response.Cancers · 2021Review
- Review
- Iron and Ferritin Modulate MHC Class I Expression and NK Cell Recognition.Frontiers in immunology · 2019Article
- Article
- Cabozantinib Eradicates Advanced Murine Prostate Cancer by Activating Antitumor Innate Immunity.Cancer discovery · 2017Article
- Influences of BRAF Inhibitors on the Immune Microenvironment and the Rationale for Combined Molecular and Immune Targeted Therapy.Current oncology reports · 2016Review
- Article
Corrections and comments
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Authors and funding
13 authors at 7 institutions in 4 countries.
Funding
Abstract
The frequent development of drug resistance to targeted therapies in cancer patients has stimulated interest in strategies counteracting resistance. Combining immunotherapies with targeted therapies is one such strategy. In this context, we asked whether human NK cells can target melanoma cells that have acquired resistance to selective inhibitors targeting activating mutants of the B-Raf kinase (BRAF inhibitors, BRAFi). We generated drug-resistant cell variants in vitro from human BRAF-mutant melanoma cell lines MEL-HO, COLO-38, SK-MEL-37, 1520 and from primary melanoma cells freshly isolated from two patients. All drug-resistant cell variants remained susceptible to lysis by IL-2-activated NK cells; and two BRAFi-resistant lines (BRAFi-R) became significantly more susceptible to NK-cell lysis than their parental lines. This was associated with significant HLA class I antigen downregulation and PD-L1 upregulation on the drug-resistant lines. Although blocking HLA class I enhanced the extent of lysis of both BRAFi-R and parental cells to NK-cell-mediated lysis, antibody-mediated inhibition of PD1-PD-L1 interactions had no detectable effect. HLA class I antigen expression on BRAFi-R melanoma variants thus appears to play a major role in their susceptibility to NK-cell cytotoxicity. These findings suggest that NK-cell-based immunotherapy may be a viable approach to treat melanoma patients with acquired resistance to BRAF inhibitors.
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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.