骨髓
多发性骨髓瘤
环钻
病理
间质细胞
肿瘤微环境
不确定意义的单克隆抗体病
活检
医学
癌症研究
生物
单克隆
免疫系统
免疫学
单克隆抗体
抗体
作者
Yeman Brhane Hagos,Catherine Lecat,Dominic Patel,Anna Mikolajczak,Simón P. Castillo,Ernst Lyon,Kane Foster,Thien-An Tran,Lydia Lee,Manuel Rodríguez-Justo,Kwee Yong,Yinyin Yuan
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2023-11-14
标识
DOI:10.1158/0008-5472.can-22-2654
摘要
Bone marrow trephine biopsy is crucial for the diagnosis of multiple myeloma. However, the complexity of bone marrow cellular, morphological, and spatial architecture preserved in trephine samples hinders comprehensive evaluation. To dissect the diverse cellular communities and mosaic tissue habitats, we developed a superpixel-inspired deep learning method (MoSaicNet) that adapts to complex tissue architectures and a cell imbalance aware deep learning pipeline (AwareNet) to enable accurate detection and classification of rare cell types in multiplex immunohistochemistry images. MoSaicNet and AwareNet achieved an area under the curve of >0.98 for tissue and cellular classification on separate test datasets. Application of MoSaicNet and AwareNet enabled investigation of bone heterogeneity and thickness as well as spatial histology analysis of bone marrow trephine samples from monoclonal gammopathies of undetermined significance (MGUS) and from paired newly diagnosed and post-treatment multiple myeloma. The most significant difference between MGUS and newly diagnosed multiple myeloma (NDMM) samples was not related to cell density but to spatial heterogeneity, with reduced spatial proximity of BLIMP1+ tumor cells to CD8+ cells in MGUS compared with NDMM samples. Following treatment of multiple myeloma patients, there was a reduction in the density of BLIMP1+ tumor cells, effector CD8+ T cells, and T regulatory cells, indicative of an altered immune microenvironment. Finally, bone heterogeneity decreased following treatment of MM patients. In summary, deep-learning based spatial mapping of bone marrow trephine biopsies can provide insights into the cellular topography of the myeloma marrow microenvironment and complement aspirate-based techniques.
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