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The administration of -expanded Natural Killer (NK) cells in leukemia therapy is still challenging, in part due to the difficulty to generate in sufficient quantities fully mature and functional NK cells and Identification of surface markers indicative of NK maturation and functionality is therefore needed. Here, based on the analysis of surface receptors of -expanded NK cells, we identified CD94 as a surface marker correlating with high lytic potential against leukemic cell lines and immunological synapse formation. CD94-positive -expanded NK cells displayed higher expression of NKG2 receptors and the adhesion molecule LFA-1, as compared with their CD94-negative counterparts. We also tested the anti-leukemic capacity of -expanded NK cells against patient-derived acute myeloid leukemia cells. Although no anti-leukemic effect was detected, we noticed that only CD94-positive -expanded NK cells were detected in leukemic mice at the end of the 2-week treatment. Moreover, flow cytometry analysis showed a subpopulation harboring CD94 (NK) and CD34 (leukemic cells) double staining, indicative of conjugate formation. Therefore surface expression of CD94 on -differentiated NK cells emerged as an indicator of and killer cell functionality.
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http://dx.doi.org/10.1080/2162402X.2017.1346763 | DOI Listing |
EMBO J
September 2025
Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA, 94720, USA.
A variety of stressors, including environmental insults, pathological conditions, and transition states, constantly challenge cells that, in turn, activate adaptive responses to maintain homeostasis. Mitochondria have pivotal roles in orchestrating these responses that influence not only cellular energy production but also broader physiological processes. Mitochondria contribute to stress adaptation through mechanisms including induction of the mitochondrial unfolded protein response (UPR) and the integrated stress response (ISR).
View Article and Find Full Text PDFCancer Metastasis Rev
September 2025
Institute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CEA, CNRS, Gif-Sur-Yvette, 91198, France.
Integrins constitute a large and diverse family of cell adhesion molecules that play essential roles in regulating tumor cell differentiation, migration, proliferation, and neovascularization. Tumor cell-derived exosomes, a subtype of extracellular vesicles, are enriched with integrins that reflect their cells of origin. These exosomal integrins can promote extracellular matrix remodeling, immune suppression, and vascular remodeling and are closely linked to tumor progression and metastasis, acting as pivotal players in mediating organ-specific metastasis.
View Article and Find Full Text PDFEMBO Mol Med
September 2025
Institute for Regenerative Medicine, Medical Innovation Center and State Key Laboratory of Cardiovascular Diseases, Shanghai East Hospital, National Stem Cell Translational Resource Center & Ministry of Education Stem Cell Resource Center, Frontier Science Center for Stem Cell Research, School of Li
Primary microcephaly, a rare congenital condition characterized by reduced brain size, occurs due to impaired neurogenesis during brain development. Through whole-exome sequencing, we identified compound heterozygous loss-of-function mutations in CENTRIN 3 (CETN3) in a 5-year-old patient with primary microcephaly. As CETN3 has not been previously linked to microcephaly, we investigated its potential function in neurodevelopment in human pluripotent stem cell-derived cerebral organoids.
View Article and Find Full Text PDFExp Neurobiol
August 2025
Institute of Medical Science, Ajou University School of Medicine, Suwon 16499, Korea.
Neural tumors represent diverse malignancies with distinct molecular profiles and present particular challenges due to the blood-brain barrier, heterogeneous molecular etiology including epigenetic dysregulation, and the affected organ's critical nature. KCC-07, a selective and blood-brain barrier penetrable MBD2 (methyl CpG binding domain protein 2) inhibitor, can suppress tumor development by inducing p53 signaling, proven only in medulloblastoma. Here we demonstrate KCC-07 treatment's application to other neural tumors.
View Article and Find Full Text PDFAm J Transplant
September 2025
Center for Transplantation Sciences, Massachusetts General Hospital, Harvard Medical School; Department of Surgery, Massachusetts General Hospital, Harvard Medical School; Department of Surgery, Hospital of the University of Pennsylvania, Perelman School of Medicine at the University of Pennsylvania
Achieving immune tolerance is a key goal in organ transplantation, as it eliminates the need for long-term immunosuppression. Regulatory B cells (Bregs) present a promising strategy for inducing tolerance. Our previous findings demonstrate that the adoptive transfer of ex vivo-expanded murine splenic B regulatory cells, referred to as TLR-Bregs (TLR9/TLR4 stimulation), induces tolerance to allografts.
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