Imaging mass cytometry(IMC)enables the high-resolution spatial profiling of tumor microenvironment,but its clinical utility for prospective prediction remains underdeveloped.In this study,we integrated IMC into a clin...Imaging mass cytometry(IMC)enables the high-resolution spatial profiling of tumor microenvironment,but its clinical utility for prospective prediction remains underdeveloped.In this study,we integrated IMC into a clinical trial of hepatocellular carcinoma(HCC)patients undergoing combination therapy with programmed death-1 blockade and transarterial chemoembolization.We analyzed 281 regions of interest from 43 patients using a custom 40-marker IMC panel and developed a novel superpixel-based graph attention network,IMCSGAT,to model spatial cell interactions within the tumor microenvironment.IMCSGAT enabled accurate multitask prediction of key clinical features,including Barcelona Clinic Liver Cancer stage,trabecular histologic subtype,and treatment response.Compared to state-of-the-art methods,IMCSGAT achieved superior performance across all classification tasks.Spatial interaction analysis revealed that resident macrophage-centered interactions,particularly those with NK and T cells,were enriched in responders and predictive of therapeutic outcome.These findings were validated in a murine HCC model,reinforcing the role of innate immune architecture in shaping the treatment response.This study establishes IMCSGAT as a powerful spatial learning framework for high-dimensional IMC data,with potential applications in clinical outcome prediction and personalized therapy design for HCC.Our results provide a blueprint for the broader use of spatial analytics in precision oncology.展开更多
Mass cytometry(cytometry by time-of-flight(CyTOF))and imaging mass cytometry(IMC)are transformative technologies that combine flow cytometry principles with time-of-flight mass spectrometry(TOF-MS).By employing metal ...Mass cytometry(cytometry by time-of-flight(CyTOF))and imaging mass cytometry(IMC)are transformative technologies that combine flow cytometry principles with time-of-flight mass spectrometry(TOF-MS).By employing metal isotope-tagged antibodies instead of fluorophores,these techniques overcome spectral overlap limitations and enable high-dimensional,compensation-free analysis of complex biological systems at single-cell resolution.The performance of CyTOF and IMC critically depends on advanced nanomaterials labeled with stable metal isotopes,which are essential for improving sensitivity and multiplexing capacity.This review systematically discusses the design principles,synthesis methods,and functionalization strategies of mass-tagged nanomaterials tailored for CyTOF(e.g.,cell suspension analysis)and IMC(e.g.,spatial proteomics of tissue sections).We highlight their impactful applications in biomedicine,including proteomics,immunology,oncology,and neuroscience,emphasizing their roles in disease diagnosis,targeted drug development,and singlecell analysis.Despite these advancements,challenges such as nanomaterial biocompatibility,clinical scalability,and artificial intelligence(AI)-driven design are discussed,providing a roadmap for future research in personalized medicine and theranostics.展开更多
In the tumor microenvironment(TME),various types of immune cells interact with each other and with cancer cells,playing critical roles in cancer progression and treatment[1].Numerous studies have reported that the inf...In the tumor microenvironment(TME),various types of immune cells interact with each other and with cancer cells,playing critical roles in cancer progression and treatment[1].Numerous studies have reported that the infiltration levels of specific immune cells are associated with patient prognosis and response to immunotherapies[2,3].展开更多
基金supported by the National Natural Science Foundation of China(grant 62136004 to D.Z.,grant 62272226 to W.S.,and grant 82173078 to J.S.)the National Key Research and Development Program of China(grant 2019YFA0803000 to J.S.)+1 种基金the Excellent Youth Foundation of Zhejiang Scientific(grant R22H1610037 to J.S.)the Zhejiang Provincial Natural Science Foundation(grant 2022C03037 to J.S.).
文摘Imaging mass cytometry(IMC)enables the high-resolution spatial profiling of tumor microenvironment,but its clinical utility for prospective prediction remains underdeveloped.In this study,we integrated IMC into a clinical trial of hepatocellular carcinoma(HCC)patients undergoing combination therapy with programmed death-1 blockade and transarterial chemoembolization.We analyzed 281 regions of interest from 43 patients using a custom 40-marker IMC panel and developed a novel superpixel-based graph attention network,IMCSGAT,to model spatial cell interactions within the tumor microenvironment.IMCSGAT enabled accurate multitask prediction of key clinical features,including Barcelona Clinic Liver Cancer stage,trabecular histologic subtype,and treatment response.Compared to state-of-the-art methods,IMCSGAT achieved superior performance across all classification tasks.Spatial interaction analysis revealed that resident macrophage-centered interactions,particularly those with NK and T cells,were enriched in responders and predictive of therapeutic outcome.These findings were validated in a murine HCC model,reinforcing the role of innate immune architecture in shaping the treatment response.This study establishes IMCSGAT as a powerful spatial learning framework for high-dimensional IMC data,with potential applications in clinical outcome prediction and personalized therapy design for HCC.Our results provide a blueprint for the broader use of spatial analytics in precision oncology.
基金supported by National Natural Science Foundation of China(T2122002,82361148715,22077079,82204104)National Key R&D Program of China(2022YFC2601700,2022YFF0710202 and 2022YFA1104200)+4 种基金Princess Nourah bint Abdulrahman University Researchers Supporting Project number(PNURSP2024R122)Shanghai Municipal Science and Technology Projects(22Z510202478)Shanghai Municipal Education Commission Projects(21SG10,ZXWH1082101)Shanghai Jiao Tong University Projects(YG2021ZD19)Shanghai University of Medicine&Health Sciences Project(AMSCP-24-07-01).
文摘Mass cytometry(cytometry by time-of-flight(CyTOF))and imaging mass cytometry(IMC)are transformative technologies that combine flow cytometry principles with time-of-flight mass spectrometry(TOF-MS).By employing metal isotope-tagged antibodies instead of fluorophores,these techniques overcome spectral overlap limitations and enable high-dimensional,compensation-free analysis of complex biological systems at single-cell resolution.The performance of CyTOF and IMC critically depends on advanced nanomaterials labeled with stable metal isotopes,which are essential for improving sensitivity and multiplexing capacity.This review systematically discusses the design principles,synthesis methods,and functionalization strategies of mass-tagged nanomaterials tailored for CyTOF(e.g.,cell suspension analysis)and IMC(e.g.,spatial proteomics of tissue sections).We highlight their impactful applications in biomedicine,including proteomics,immunology,oncology,and neuroscience,emphasizing their roles in disease diagnosis,targeted drug development,and singlecell analysis.Despite these advancements,challenges such as nanomaterial biocompatibility,clinical scalability,and artificial intelligence(AI)-driven design are discussed,providing a roadmap for future research in personalized medicine and theranostics.
基金supported by the Cancer Prevention Research Institute of Texas(CPRIT)(RR180061)the National Cancer Institute of the National Institute of Health(1R01CA269764).
文摘In the tumor microenvironment(TME),various types of immune cells interact with each other and with cancer cells,playing critical roles in cancer progression and treatment[1].Numerous studies have reported that the infiltration levels of specific immune cells are associated with patient prognosis and response to immunotherapies[2,3].
