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Background: Gamma-delta (γδ) T lymphocytes are primed to potently respond to pathogens and transformed cells by recognizing a broad range of antigens. However, adoptive immunotherapy with γδT cells has exhibited mixed treatment responses. Better understanding of γδT cell biology and stratifying healthy donors for allogeneic adoptive therapy is clinically needed to fully realize the therapeutic potential of γδT cells.
Methods: We examine 98 blood samples from healthy donors and measure their expansion capacity after zoledronate stimulation, and test the migration and cytotoxic effector function of expanded γδT cells in 2D culture, 3D tumor spheroid and patient-derived melanoma organoid assays.
Results: We find that γδT cell expansion capacity is independent of expansion methods, gender, age and HLA type. Basal γδT cell levels in Peripheral blood mononuclear cell (PBMC) correlate well with their expansion, migration and cytotoxic effector capacity in vitro. Circulating γδT cells with lower expression of PD-1, CTLA-4, Eomes, T-bet and CD69, or higher IFN-γ production expand better. γδT cells with central memory and effector memory phenotypes are significantly more abundant in good expanders. A cut-off level of 0.82% γδT cells in PBMC stratifies good versus poor γδT cell expansion with a sensitivity of 97.78%, specificity of 90.48% and area under the curve of 0.968 in a healthy individual. Donors with higher Vδ2 Index Score in PBMC have greater anti-tumor functions including migratory function and cytotoxicity.
Conclusions: Our results demonstrate that the interindividual γδT cell functions correlate with their circulating levels in healthy donors. Examination of circulating γδT cell level may be used to select healthy donors to participate in γδT-based immunotherapies.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137237 | PMC |
http://dx.doi.org/10.1136/jitc-2020-002274 | DOI Listing |
ACS Chem Neurosci
December 2024
Department of Chemistry and Biochemistry, University of Denver, Denver, Colorado 80210, United States.
The formation of Lewy bodies (LB) is a pathological hallmark for synucleinopathies, which is an umbrella term for many diseases, including Parkinson's disease, Lewy body dementia, and multiple system atrophy. One of the main components of LB is the aggregates of phosphorylated modification of α-Synuclein at residue 129 (αS-129), a neuronal protein expressed in the dopaminergic neurons in the brain. There are equivocal results about the role of αS-129, suggesting its involvement in both potentiating pathology and a functional role to rescue pathology.
View Article and Find Full Text PDFJ Int Med Res
December 2024
Department of Hematology, The First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, China.
Objective: Mobilization and collection of peripheral blood stem cells (PBSCs) are time-intensive and costly. Excessive apheresis sessions can cause physical discomfort for donors and increase the costs associated with collection. Therefore, it is essential to identify key predictive factors for successful harvests to minimize the need for multiple apheresis procedures.
View Article and Find Full Text PDFJ Int Med Res
December 2024
Department of Urology, Shaoxing People's Hospital, Shaoxing, Zhejiang, China.
renal transplant carcinoma, especially in the context of bilateral renal carcinoma, is rare and often presents as small, low-grade papillary renal cell carcinoma (RCC). There is currently no consensus or effective treatment for advanced metastatic RCC after kidney transplantation. A 40-year-old man developed renal transplant carcinoma with venous thrombus and lung metastases 13 years after transplantation.
View Article and Find Full Text PDFJ Int Med Res
December 2024
Department of Oncology Medicine, Affiliated Zhongshan Hospital of Dalian University, Dalian, China.
Small cell lung cancer (SCLC) is an aggressive neuroendocrine tumor with the poorest prognosis among all types of lung cancer. Developing an effective comprehensive strategy remains a key focus. We herein present the first documented case of a 68-year-old man with limited-stage SCLC who has maintained a complete response (CR) for over 30 months to date.
View Article and Find Full Text PDFJ Am Chem Soc
December 2024
Department of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul 08826, Republic of Korea.
Electrochemical liquid-cell transmission electron microscopy (e-LCTEM) offers great potential for investigating the structural dynamics of nanomaterials during electrochemical reactions. However, challenges arise from the difficulty in achieving the optimal electrolyte thickness, leading to inconsistent electrochemical responses and limited spatial resolution. In this study, we present advanced e-LCTEM techniques tailored for tracking Pt/C degradation under electrochemical polarization at short intervals with high spatial resolution.
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