肿瘤细胞治疗研究
英文原题：Single-cell RNA sequencing defines distinct disease subtypes and reveals hypo-responsiveness to interferon in asymptomatic Waldenstrom's Macroglobulinemia.
为了剖析肿瘤内在和免疫进展机制，我们对来自30名AWM/WM患者、26名冒烟型骨髓瘤患者和23名健康供者的294,206个BM肿瘤和免疫细胞进行了单细胞RNA测序。
华氏巨球蛋白血症（WM）是一种分泌IgM的骨髓（BM）淋巴瘤，其前驱阶段为无症状状态（AWM）。为剖析肿瘤内在及免疫介导的进展机制，我们对来自30例AWM/WM患者、26例冒烟型骨髓瘤患者和23例健康供者的294,206个BM肿瘤细胞和免疫细胞进行了单细胞RNA测序。尽管处于早期阶段，AWM患者已表现出广泛的免疫失调，包括正常B细胞，并具有疾病特异性免疫标志。患者的T细胞和NK细胞对干扰素表现出系统性低反应性，给予干扰素后可改善，这可能代表一种治疗脆弱性。MYD88突变肿瘤表现出转录异质性，可归纳为一种分子分类，包括DUSP22/CD9阳性亚型，以及可区分IgM MGUS与显性WM的进展特征，有助于推动WM研究和临床实践。
Waldenstrom's Macroglobulinemia (WM) is an IgM-secreting bone marrow (BM) lymphoma that is preceded by an asymptomatic state (AWM). To dissect tumor-intrinsic and immune mechanisms of progression, we perform single-cell RNA-sequencing on 294,206 BM tumor and immune cells from 30 patients with AWM/WM, 26 patients with Smoldering Myeloma, and 23 healthy donors. Despite their early stage, patients with AWM present extensive immune dysregulation, including in normal B cells, with disease-specific immune hallmarks. Patient T and NK cells show systemic hypo-responsiveness to interferon, which improves with interferon administration and may represent a therapeutic vulnerability. MYD88-mutant tumors show transcriptional heterogeneity, which can be distilled in a molecular classification, including a DUSP22/CD9-positive subtype, and progression signatures which differentiate IgM MGUS from overt WM and can help advance WM research and clinical practice.
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