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Background: The use of natural killer (NK) cells is a promising approach in the field of cancer immunotherapy; however, combination treatments are required to enhance the effects of NK cell immunotherapy. In this study, we assessed the potential of irradiation and cisplatin as a chemoradiotherapy (CRT) regimen to augment the effects of NK cell immunotherapy in head and neck squamous cell carcinoma (HNSCC).
Methods: NK cells were expanded using our recently established K562-OX40 ligand and membrane-bound interleukin (IL)-18 and IL-21 feeder cells in the presence of IL-2/IL-15 from peripheral blood of healthy donors.
Results: The results showed an increase in the purity of NK cells and expression of activation markers such as NKG2D and lymphocyte function-associated antigen 1 during the expansion process, which is positively correlated to the NK cell infiltration and overall survival in patients with HNSCC. CRT induced NK cell activation ligand (ULBP2) and adhesion molecules (ICAM-1, -2 and -3) on HNSCC, leading to enhanced cytotoxicity of NK cells against HNSCC.
Conclusions: Our findings suggest that the NK cells have a potent anti-tumor effect in combination with CRT against HNSCC.
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http://dx.doi.org/10.1016/j.jcyt.2022.05.004 | DOI Listing |
Nature
September 2025
Marc and Jennifer Lipschultz Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Monocyte-derived macrophages (mo-macs) often drive immunosuppression in the tumour microenvironment (TME) and tumour-enhanced myelopoiesis in the bone marrow fuels these populations. Here we performed paired transcriptome and chromatin accessibility analysis over the continuum of myeloid progenitors, circulating monocytes and tumour-infiltrating mo-macs in mice and in patients with lung cancer to identify myeloid progenitor programs that fuel pro-tumorigenic mo-macs. We show that lung tumours prime accessibility for Nfe2l2 (NRF2) in bone marrow myeloid progenitors as a cytoprotective response to oxidative stress, enhancing myelopoiesis while dampening interferon response and promoting immunosuppression.
View Article and Find Full Text PDFJ Immunother Cancer
September 2025
Harold C Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas, USA
Background: While highly efficacious for numerous cancers, immune checkpoint inhibitors (ICIs) can cause unpredictable and potentially severe immune-related adverse events (irAEs), underscoring the need to understand irAE biology.
Methods: We used a multidimensional approach incorporating single-cell RNA sequencing, mass cytometry, multiplex cytokine assay, and antinuclear antibody (ANA) profiling to characterize the peripheral immune landscape of patients receiving ICI therapy according to irAE development.
Results: Analysis of 162 patients revealed that individuals who developed clinically significant irAEs exhibited a baseline proinflammatory, autoimmune-like state characterized by a significantly higher abundance of CD57 T and natural killer (NK) T cells, plasmablasts, proliferating and activated CXCR3 lymphocytes, CD8 effector and terminal effector memory T cells, along with reduced NK cells and elevated plasma ANA levels.
J Immunother Cancer
September 2025
Division of Hematology & Oncology, Department of Medicine, School of Medicine, University of California, Irvine, California, USA
Background: γδ T cells possess unique immunological features including tissue tropism, major histocompatibility complex-independent antigen recognition, and hybrid T/natural killer cell properties that make them promising candidates for cancer immunotherapy. However, the therapeutic potential of Vδ1 γδ T cells, particularly when engineered with chimeric antigen receptors (CARs), remains underexplored in solid tumors such as pancreatic cancer (PC), largely due to their low abundance in peripheral blood and challenges in ex vivo expansion. This study aims to directly compare the preclinical safety and efficacy among CAR-engineered Vδ1 γδ T cells, Vδ2 γδ T cells, and conventional αβ T cells.
View Article and Find Full Text PDFBrain Behav Immun
September 2025
Centre for Genomic Regulation (CRG), The Barcelona Institute for Science and Technology (BIST), Barcelona, Spain; Universitat Pompeu Fabra (UPF), Barcelona, Spain; Biomedical Research Networking Center for Rare Diseases (CIBERER), Barcelona 08003, Spain.
Treatment-resistant depression (TRD) is a severe condition characterized by chronic and recurrent depressive symptoms, leading to significant morbidity and a considerable socio-economic impact. Genetic and biological studies suggest that TRD is associated with distinct biological characteristics. In this study, we analysed whole-transcriptome differences in 293 patients with major depressive disorder (MDD) to compare TRD (N = 150) vs non-TRD (N = 143) cases.
View Article and Find Full Text PDFJ Leukoc Biol
September 2025
Laboratory of Immunobiology and Ionic Transport Regulation, Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Av. 25 de Julio 965, Villa de San Sebastián, 28045 Colima, México.
Ion channels are integral membrane proteins which facilitate rapid transport of small ions into and out of the cell and between organelles and cytosol. Cytolytic lymphocytes including natural killer (NK) cells principally kill virus-infected and cancer cells by releasing cytolytic granules within the immunological synapse, formed between target and effector cells. This process strongly depends on Ca2+ signaling, which in human NK cells is controlled by the phospholipase C (PLCγ)/inositol-1,4,5-triphospate receptor (IP3R)/calcium release-activated calcium channel (CRAC) axis.
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