摘要
The pathogenesis of neuroblastoma with bone or bone marrow metastasis (NB-BBM)and its complex immune microenvironment remain poorly elucidated, hampering the advancement of effective risk prediction for BBM and limiting therapeutic strategies. Feature recognition of 142 paraffin-embedded hematoxylin-eosin-stained tumor section images was conductedusing a Swin-Transformer for pathological histology to predict NB-BBM occurrence. Single-celltranscriptomics identified a tumor cell subpopulation (NB3) and two tumor-associated macrophage (TAM) subpopulations (SPP1^(+) TAMs and IGHM^(+) TAMs) closely associated with BBM andhighlighted transketolase (TKT) as a key molecular marker for metastatic progression in NB.This extensive multi-omics investigation into NB-BBM enhances our understanding of single-celltranscriptional dynamics in NB beyond existing research, outlining the evolution from in situcarcinoma through tumorigenesis to bone marrow metastases. Furthermore, exploration ofthe immune microenvironment identified specific subpopulations of TAMs crucial in promotingNB-BBM, presenting new avenues for immunotherapy. These insights enhance our understanding of the metastatic process from NB to BBM and facilitate the development of more effectivediagnostic and therapeutic strategies for this aggressive pediatric cancer.
基金
supported in part by research grants from the Key Project of the National Key R&D Plan“Research on Prevention and Control of Major Chronic Non-Communicable Diseases”(China)
the Ministry of Science and Technology of the People’s Republic of China,and the National Key R&D Program of China(No.2018YFC1313000,2018YFC1313004).
