Enriched Adaptive Immunity and Reduced Inflammatory Response in Plasma Cell Disorders of Self-Identified Black Patients

IF 23.9 1区医学 Q1 HEMATOLOGY

Blood Pub Date : 2026-10-05 DOI:10.1182/blood.2026033998

Hongwei Tang,William C Pilcher,Huihuang Yan,Annamalai Sivasankar,Jinzhuang Dou,Suganti Shivaram,Mariam Khanfar,Neeraj Sharma,Stacey J. Lehman,Shulan Tian,Surendra Dasari,Cinthya J Zepeda-Mendoza,Mahek Bai,Joselle Cook,Nadine Abdallah,Abiola Bolarinwa,Emilie I Anderson,Taxiarchis V. Kourelis,S Vincent Rajkumar,Shaji K. Kumar,Megan Weivoda,Felicia Gomez,Manoj Bhasin,Linda B Baughn

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引用次数: 0

Abstract

The immune tumor microenvironment (iTME) plays a crucial role in disease biology of plasma cell (PC) dyscrasias, but remains poorly characterized in self-identified Black individuals, a population at increased risk. Mass cytometry and scRNA-seq of 128 bone marrow aspirates revealed significant changes in immune cell composition across the disease spectrum, including shifts from naïve to effector T cells with declines in B cells, MAIT, pDCs, and increases in monocytes with disease progression. Self-identified Black patients had higher relative proportions of terminally differentiated T cells and lower monocytes in newly diagnosed and treated multiple myeloma (MM). ScRNA-seq revealed genes overexpressed in self-identified Black individuals were enriched for E2F targets and G2-M checkpoints, while reduced genes were enriched for TNF-α/NF-kB, interferon and inflammatory responses pathways. These findings were supported by genetic ancestry and validated in an independent dataset of 286 patients with MM from the MMRF Immune Atlas. Self-identified race and African genetic similarity are significantly associated with remodeling the MM iTME, with potential implications for disease biology and treatment response.

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自我鉴定的黑人患者浆细胞疾病的适应性免疫增强和炎症反应降低

免疫肿瘤微环境（iTME）在浆细胞（PC）异常的疾病生物学中起着至关重要的作用，但在自我认定的黑人个体中仍然缺乏特征，这是一个风险增加的人群。128例骨髓抽液的质量细胞术和scRNA-seq显示，在整个疾病谱系中，免疫细胞组成发生了显著变化，包括从naïve到效应T细胞的转变，B细胞、MAIT、pDCs减少，单核细胞随着疾病进展而增加。在新诊断和治疗的多发性骨髓瘤（MM）中，自认为黑人的患者终末分化T细胞相对比例较高，单核细胞相对比例较低。ScRNA-seq显示，在自我鉴定的黑人个体中，E2F靶点和G2-M检查点的过表达基因富集，而TNF-α/NF-kB、干扰素和炎症反应途径的过表达基因富集。这些发现得到了遗传祖先的支持，并在来自MMRF免疫图谱的286例MM患者的独立数据集中得到了验证。自我识别的种族和非洲遗传相似性与MM iTME重塑显着相关，对疾病生物学和治疗反应具有潜在意义。

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来源期刊

Blood 医学-血液学

CiteScore

23.60

自引率

3.90%

发文量

955

审稿时长

1 months

期刊介绍： Blood, the official journal of the American Society of Hematology, published online and in print, provides an international forum for the publication of original articles describing basic laboratory, translational, and clinical investigations in hematology. Primary research articles will be published under the following scientific categories: Clinical Trials and Observations; Gene Therapy; Hematopoiesis and Stem Cells; Immunobiology and Immunotherapy scope; Myeloid Neoplasia; Lymphoid Neoplasia; Phagocytes, Granulocytes and Myelopoiesis; Platelets and Thrombopoiesis; Red Cells, Iron and Erythropoiesis; Thrombosis and Hemostasis; Transfusion Medicine; Transplantation; and Vascular Biology. Papers can be listed under more than one category as appropriate.