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Antagonistic anti-LILRB1 monoclonal antibody regulates antitumor functions of natural killer cells

Current immune checkpoint blockade strategies have been successful in treating certain types of solid cancer. However, checkpoint blockade monotherapies have not been successful against most hematological malignancies including multiple myeloma and leukemia. LILRB1, an immunoreceptor tyrosine...

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Nectin4 is a novel TIGIT ligand which combines checkpoint inhibition and tumor specificity

The use of checkpoint inhibitors has revolutionized cancer therapy. Unfortunately, these therapies often cause immune-related adverse effects, largely due to a lack of tumor specificity. The authors discovered that Nectin4 is a novel ligand for TIGIT and demonstrated that specific antibodies...

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IL-15 superagonist RLI has potent immunostimulatory properties on NK cells: implications for antimetastatic treatment

As the immune system is compromised in patients with cancer, therapeutic strategies to stimulate immunity appear promising, to avoid relapse and increase long-term overall survival. Interleukin-15 (IL-15) has similar properties to IL-2, but does not cause activation-induced cell death nor...

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PD-L1 targeting high-affinity NK (t-haNK) cells induce direct antitumor effects and target suppressive MDSC populations

Although immune checkpoint inhibitors have revolutionized cancer treatment, clinical benefit with this class of agents has been limited to a subset of patients. Hence, more effective means to target tumor cells that express immune checkpoint molecules should be developed. The authors report a...

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Overcoming hypoxia-induced functional suppression of NK cells

Natural killer (NK) cells are immune cells capable of killing virally infected cells and tumor cells without the need for antigen stimulation. Tumors, however, can create a suppressive microenvironment that decreases NK function. A feature of many tumors is hypoxia (low oxygen perfusion), which...

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Immunogenicity of cell death driven by immune effectors

Whether cell death caused by T lymphocytes and natural killer (NK) cells would be immunogenic per se has been a matter of intense debate. Two back-to-back papers from the Melero’s and Pardo’s groups have now resolved this conundrum, demonstrating that T and NK cell–mediated cytotoxicity...

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Longitudinal NK cell kinetics and cytotoxicity in children with neuroblastoma enrolled in a clinical phase II trial

Natural killer (NK) cells are one of the main effector populations of immunotherapy with monoclonal antibody and cytokines, used in combination with chemotherapy to treat children with high-risk neuroblastoma on this phase II trial. However, the impact of chemoimmunotherapy on NK cell kinetics,...

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CCL5-armed oncolytic virus augments CCR5-engineered NK cell infiltration and antitumor efficiency

Natural killer (NK) cells have potent antitumor activities. Nevertheless, adoptive transfer therapy of NK cells has gained very limited success in patients with solid tumors as most infused NK cells remain circulating in the peripheral blood instead of entering tumor sites. Chemokines and their...

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Targeting of CXCR3 improves anti-myeloma efficacy of adoptively transferred activated natural killer cells

The peculiar multiple myeloma microenvironment, characterized by up-regulated levels of several inflammatory chemokines, including the CXCR3 receptor ligands CXCL9 and CXCL10, limits NK cell positioning into the bone marrow by interfering with CXCR4 function. It is still unclear if the...