Infection is the leading cause of death in multiple myeloma (MM). However, the cellular composition associated with immune dysfunction is not defined. We analyzed immune profiles in the peripheral blood of patients with MM (n = 28) and B-cell chronic lymphoproliferative disorders (n = 53) vs. health care practitioners (n = 96), using multidimensional and computational flow cytometry. MM patients displayed altered distribution of most cell types (41/56, 73%), particularly within the B-cell (17/17) and T-cell (20/30) compartments. Using COVID-19 as a case study, we compared the immune response to vaccination based on 64,304 data points generated from the analysis of 1099 longitudinal samples. MM patients showed limited B-cell expansion linked to lower anti-RBD and anti-S antibody titers after the first two doses and booster. The percentages of B cells and CD4+ T cells in the blood, as well as the absolute counts of B cells and dendritic cells, predicted vaccine immunogenicity at different time points. In contrast with the humoral response, the percentage and antigen-dependent differentiation of SARS-CoV-2-specific CD8+ T cells was not altered in MM patients. Taken together, this study defined the cellular composition associated with immune dysfunction in MM and provided biomarkers such as the B-cell percentage and absolute count to individualize vaccination calendars.
感染是多发性骨髓瘤（MM）患者的主要死亡原因。然而，与免疫功能障碍相关的细胞组成尚未明确。我们采用多维计算流式细胞术，分析了多发性骨髓瘤患者（n=28）、B细胞慢性淋巴增殖性疾病患者（n=53）与医护人员（n=96）的外周血免疫图谱。结果显示，多发性骨髓瘤患者大多数细胞类型（41/56，73%）的分布发生改变，尤其在B细胞（17/17）和T细胞（20/30）区段中表现显著。
以COVID-19为案例，我们基于1,099份纵向样本分析产生的64,304个数据点，比较了不同群体的疫苗接种免疫反应。多发性骨髓瘤患者在前两剂及加强针接种后，显示出有限的B细胞扩增，且与较低的抗RBD和抗S抗体滴度相关。血液中B细胞和CD4+ T细胞的百分比，以及B细胞和树突状细胞的绝对计数，可预测不同时间点的疫苗免疫原性。与体液免疫反应相反，多发性骨髓瘤患者中SARS-CoV-2特异性CD8+ T细胞的百分比及抗原依赖性分化能力未见异常。
综上所述，本研究明确了多发性骨髓瘤免疫功能障碍相关的细胞组成特征，并提出了如B细胞百分比和绝对计数等生物标志物，可用于制定个体化疫苗接种计划。
肿瘤(癌症)患者之家