ArticleJournal for immunotherapy of cancer2024
IFNγ mediates the resistance of tumor cells to distinct NK cell subsets.
Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Research progress on the molecular mechanisms of PD-1 and LAG-3 synergy in regulating T cell exhaustion and immunotherapy.Annals of medicine · 2026Review
- NKG2A-HLA-E axis contributes to an immunosuppressive checkpoint network in hepatocellular carcinoma.Journal for immunotherapy of cancer · 2026Article
- BAP1 loss impairs IFN-γ signaling and enhances NK cell-mediated cytotoxicity in myeloid leukemia.Cancer immunology, immunotherapy : CII · 2026Article
- Circumventing IFN-γ induced resistance in ovarian cancer with a double-hit: NKG2A knockout of PRAME-TCR expressing NK cells.Journal of ovarian research · 2026Article
- Peroxidasin enables melanoma immune escape by inhibiting natural killer cell cytotoxicity.Molecular oncology · 2026Article
- Membrane-modified mesoporous silica nanoparticles guided by tumor immunomodulatory regulation for anti-tumor strategies.Frontiers in immunology · 2026Review
- Artificial neural network-based immune biomarker signature predicts pathological complete response to neoadjuvant chemotherapy in HER2-negative breast cancer.Frontiers in oncology · 2026Article
- Cancer immunoediting in the melanoma tumor microenvironment: from immune elimination to therapeutic resistance.Frontiers in immunology · 2026Review
- Review
- The IFNγ-CIITA-MHC II axis modulates melanoma cell susceptibility to NK-cell-mediated cytotoxicity.Molecular oncology · 2025Article
- Turning the tide in peritoneal metastases: Locoregional CAR-NK therapy primes systemic immunity in colorectal cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- The Role of Tumor Microenvironment in Triple-Negative Breast Cancer and Its Therapeutic Targeting.Cells · 2025Review
- Prospects and applications of NK therapy in the treatment of gliomas (Review).Oncology reports · 2025Review
- Decoding MHC loss: Molecular mechanisms and implications for immune resistance in cancer.Clinical and translational medicine · 2025Review
- The Role of NK Cells in Cancer Immunotherapy: Mechanisms, Evasion Strategies, and Therapeutic Advances.Biomedicines · 2025Review
- Genome-wide CRISPR/Cas9 screen reveals factors that influence the susceptibility of tumor cells to NK cell-mediated killing.Journal for immunotherapy of cancer · 2025Article
- VEGF-D Dependent IFNγ Production by Natural Killer Cells in Lymphangioleiomyomatosis.Journal of cellular immunology · 2025Article
- ADCC: the rock band led by therapeutic antibodies, tumor and immune cells.Frontiers in immunology · 2025Review
- Natural Killer Cell Immune Checkpoints and Their Therapeutic Targeting in Cancer Treatment.Research (Washington, D.C.) · 2025Article
- Overcoming resistance to PD-1 and CTLA-4 blockade mechanisms and therapeutic strategies.Frontiers in immunology · 2025Review
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImmune checkpoint blockade targeting the adaptive immune system has revolutionized the treatment of cancer. Despite impressive clinical benefits observed, patient subgroups remain non-responsive underscoring the necessity for combinational therapies harnessing additional immune cells. Natural killer (NK) cells are emerging tools for cancer therapy. However, only subpopulations of NK cells that are differentially controlled by inhibitory receptors exert reactivity against particular cancer types. How to leverage the complete anti-tumor potential of all NK cell subsets without favoring the emergence of NK cell-resistant tumor cells remains unresolved.
methodsWe performed a genome-wide CRISPR/Cas9 knockout resistance screen in melanoma cells in co-cultures with human primary NK cells. We comprehensively evaluated factors regulating tumor resistance and susceptibility by focusing on NK cell subsets in an allogenic setting. Moreover, we tested therapeutic blocking antibodies currently used in clinical trials.
resultsMelanoma cells deficient in antigen-presenting or the IFNγ-signaling pathways were depleted in remaining NK cell-co-cultured melanoma cells and displayed enhanced sensitivity to NK cells. Treatment with IFNγ induced potent resistance of melanoma cells to resting, IL-2-cultured and ADCC-activated NK cells that depended on
conclusionOur data reveal that in the context of NK cells, IFNγ induces the resistance of tumor cells by the upregulation of classical and non-classical MHC-I. Moreover, we reveal insights into NK cell subset reactivity and propose a therapeutic strategy involving combinational monalizumab/lirilumab/DX9 treatment to fully restore the antitumor response across NK cell subsets.
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