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
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.
