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The natural killer (NK) group 2 member D (NKG2D) is an activating immune receptor expressed on NK cells, cytotoxic T cells and a subset of other T cells. It has an important role in the recognition and lysis of a variety of infected and tumor cells. Despite significant gains in our understanding of NKG2D, the relevance of NKG2D and its ligands in human diseases has only recently started to emerge. Here, we present an overview of the recent advances in NKG2D biology, discuss the expression of NKG2D ligands in cancer patients and evaluate the diagnostic and prognostic potential of NKG2D ligands.
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http://dx.doi.org/10.1038/icb.2013.111 | DOI Listing |
Int J Biol Macromol
September 2025
Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, 213003, China; Institute of Cell The
Despite its potential as a cancer immunotherapy, wild-type IL-2 is limited by dose-limiting toxicities, including vascular leak syndrome, and its strong activation of regulatory T cells (Tregs), which dampens anti-tumor immunity. These drawbacks are largely driven by IL-2's binding to IL-2Rα, and avoiding this interaction can reduce IL-2-associated toxicities, although it cannot completely eliminate them. To overcome these limitations, βγ-biased IL-2 variants (Non-α-IL-2) have been developed to selectively activate effector T and NK cells.
View Article and Find Full Text PDFBlood
September 2025
Hugh & Josseline Langmuir Centre for Myeloma Research, Centre for Haematology, Imperial College London, London, United Kingdom.
Current therapies, including autologous CAR-T immunotherapy, fail to cure half of infants with KMT2A-rearranged acute lymphoblastic leukemia (KMT2Ar-ALL), a disease characterized by frequent central nervous system involvement, poor treatment response, early relapse and lineage switching. More effective treatment strategies, including the availability of 'off-the-shelf' immunotherapies is particularly relevant in infants. PROM1/CD133 is a direct target of KMT2A-fusion oncoproteins and is expressed on leukemic cells.
View Article and Find Full Text PDFInt J Mol Sci
August 2025
Medical School, Department of Medical Microbiology, University of Pecs, 7624 Pecs, Hungary.
This study investigated the expression of immune checkpoint molecules on CD4 and CD4 NKT cell subpopulations throughout healthy pregnancy trimesters and in non-pregnant condition to understand their role in maternal-fetal immunotolerance. Using flow cytometry, we found that CD4 NKT cells significantly outnumbered CD4 NKT cells in all investigated groups. In the case of the immune checkpoint molecules, PD-1 receptor expression was significantly lower in CD4 NKT cells compared to CD4 counterpart cells only in non-pregnant women, while the PD-L1 ligand expression on CD4 NKT cells significantly decreased in the third trimester.
View Article and Find Full Text PDFBMC Biotechnol
August 2025
Department of Hematology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi Province, China.
Background: Natural killer (NK) cell immunotherapy is a promising approach for cancer treatment. However, its extensive clinical application was limited to the large-scale clinical-grade expansion of NK cells. In this study, we expanded NK cells from healthy donor's peripheral blood mononuclear cells (PBMCs) using a newly designed K562 feeder cell line.
View Article and Find Full Text PDFCancer Lett
August 2025
Division of Nephrology, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address:
The mechanisms underlying therapeutic resistance to c-Met/receptor tyrosine kinase (RTK) inhibitors in renal cancer remain unexplored. In renal cell carcinoma (RCC) cells, both AXL and c-Met are highly upregulated. Notably, we found that prolonged treatment with the c-Met/RTK inhibitor, cabozantinib (Cabo), a standard treatment for advanced-stage RCC, markedly increased total c-Met levels and promoted renal cancer cell proliferation.
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