Institute of Haematology, Multiple Myeloma Research Laboratory, NSW Health Pathology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; School of Life Sciences, University of Technology Sydney, Ultimo, NSW.
Institute of Haematology, Multiple Myeloma Research Laboratory, NSW Health Pathology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia; Sydney Medical School, The University of Sydney, Sydney, NSW.
Haematologica. 2024 Apr 1;109(4):1220-1232. doi: 10.3324/haematol.2023.283062.
Multiple myeloma (MM) is an incurable disease of the bone marrow (BM) characterized by the uncontrolled proliferation of neoplastic plasma cells. While CD8+ T cells have an established role in disease control, few studies have focused on these cells within the MM tumor microenvironment (TME). We analyzed CD8+ T cells in the BM and peripheral blood (PB) of untreated patients with MM and non-myeloma controls using flow cytometry, mass cytometry and single-cell RNA sequencing, using several novel bioinformatics workflows. Inter-tissue differences were most evident in the differential expression of Granzymes B and K, which were strongly associated with two distinct subsets of CD8+ T cells delineated by the expression of CD69, accounting for roughly 50% of BM-CD8+ T cells of all assessed cohorts. While few differences were observable between health and disease in the BM-restricted CD8CD69+ T-cell subset, the CD8+CD69- T-cell subset in the BM of untreated MM patients demonstrated increased representation of highly differentiated effector cells and evident compositional parallels between the PB, absent in age-matched controls, where a marked reduction of effector cells was observed. We demonstrate the transcriptional signature of BM-CD8+ T cells from patients with MM more closely resembles TCR-activated CD8+ T cells from age-matched controls than their resting counterparts.
多发性骨髓瘤（MM）是一种不可治愈的骨髓（BM）疾病，其特征是恶性浆细胞的不受控制增殖。虽然 CD8+T 细胞在疾病控制中具有既定作用，但很少有研究关注 MM 肿瘤微环境（TME）中的这些细胞。我们使用流式细胞术、质谱流式细胞术和单细胞 RNA 测序，使用几种新的生物信息学工作流程，分析了未经治疗的 MM 患者和非骨髓瘤对照者 BM 和外周血（PB）中的 CD8+T 细胞。组织间差异在 Granzymes B 和 K 的差异表达中最为明显，它们与 CD69 表达定义的两个不同的 CD8+T 细胞亚群强烈相关，占所有评估队列中 BM-CD8+T 细胞的大约 50%。虽然在 BM 受限的 CD8+CD69+T 细胞亚群中，健康和疾病之间几乎没有差异，但未经治疗的 MM 患者 BM 中的 CD8+CD69-T 细胞亚群表现出高度分化的效应细胞的代表性增加，并且与 PB 之间存在明显的组成平行，而在年龄匹配的对照中则观察到效应细胞明显减少。我们证明 MM 患者 BM-CD8+T 细胞的转录特征更类似于与年龄匹配的对照者的 TCR 激活的 CD8+T 细胞，而不是其静息对应物。
