The intricacy of diseases,shaped by intrinsic processes like immune system exhaustion and hyperactivation,highlights the potential of immune renormalization as a promising strategy in disease treatment.In recent years...The intricacy of diseases,shaped by intrinsic processes like immune system exhaustion and hyperactivation,highlights the potential of immune renormalization as a promising strategy in disease treatment.In recent years,our primary focus has centered onγδT cell-based immunotherapy,particularly pioneering the use of allogeneic Vδ2+γδT cells for treating late-stage solid tumors and tuberculosis patients.However,we recognize untapped potential and optimization opportunities to fully harnessγδT cell effector functions in immunotherapy.This review aims to thoroughly examineγδT cell immunology and its role in diseases.Initially,we elucidate functional differences betweenγδT cells and theirαβT cell counterparts.We also provide an overview of major milestones inγδT cell research since their discovery in 1984.Furthermore,we delve into the intricate biological processes governing their origin,development,fate decisions,and T cell receptor(TCR)rearrangement within the thymus.By examining the mechanisms underlying the anti-tumor functions of distinctγδT cell subtypes based onγδTCR structure or cytokine release,we emphasize the importance of accurate subtyping in understandingγδT cell function.We also explore the microenvironment-dependent functions ofγδT cell subsets,particularly in infectious diseases,autoimmune conditions,hematological malignancies,and solid tumors.Finally,we propose future strategies for utilizing allogeneicγδT cells in tumor immunotherapy.Through this comprehensive review,we aim to provide readers with a holistic understanding of the molecular fundamentals and translational research frontiers ofγδT cells,ultimately contributing to further advancements in harnessing the therapeutic potential ofγδT cells.展开更多
基金partially supported by the National Natural Science Foundation of China(82002787,Y.H.,32270950,Y.Z.W.)the Key Program of the National Natural Science Foundation of China(32030036,Z.N.Y.)+2 种基金the Startup Foundation of the Zhuhai People’s Hospital(YNXM20210305,Y.Z.W.)Y.S.L.is supported by the Major International(Regional)Joint Research Program of the National Natural Science Foundation of China(81920108027)D.K.is supported by Deutsche Forschungsge-meinschaft(Ka 502/19-3).
文摘The intricacy of diseases,shaped by intrinsic processes like immune system exhaustion and hyperactivation,highlights the potential of immune renormalization as a promising strategy in disease treatment.In recent years,our primary focus has centered onγδT cell-based immunotherapy,particularly pioneering the use of allogeneic Vδ2+γδT cells for treating late-stage solid tumors and tuberculosis patients.However,we recognize untapped potential and optimization opportunities to fully harnessγδT cell effector functions in immunotherapy.This review aims to thoroughly examineγδT cell immunology and its role in diseases.Initially,we elucidate functional differences betweenγδT cells and theirαβT cell counterparts.We also provide an overview of major milestones inγδT cell research since their discovery in 1984.Furthermore,we delve into the intricate biological processes governing their origin,development,fate decisions,and T cell receptor(TCR)rearrangement within the thymus.By examining the mechanisms underlying the anti-tumor functions of distinctγδT cell subtypes based onγδTCR structure or cytokine release,we emphasize the importance of accurate subtyping in understandingγδT cell function.We also explore the microenvironment-dependent functions ofγδT cell subsets,particularly in infectious diseases,autoimmune conditions,hematological malignancies,and solid tumors.Finally,we propose future strategies for utilizing allogeneicγδT cells in tumor immunotherapy.Through this comprehensive review,we aim to provide readers with a holistic understanding of the molecular fundamentals and translational research frontiers ofγδT cells,ultimately contributing to further advancements in harnessing the therapeutic potential ofγδT cells.
