Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH, United States.
Comprehensive Cancer Center, The Ohio State University, Columbus, OH, United States.
Front Immunol. 2021 Sep 3;12:700045. doi: 10.3389/fimmu.2021.700045. eCollection 2021.
We report a first in-depth comparison of immune reconstitution in patients with HIV-related lymphoma following autologous hematopoietic cell transplant (AHCT) recipients (n=37, lymphoma, BEAM conditioning), HIV(-) AHCT recipients (n=30, myeloma, melphalan conditioning) at 56, 180, and 365 days post-AHCT, and 71 healthy control subjects. Principal component analysis showed that immune cell composition in HIV(+) and HIV(-) AHCT recipients clustered away from healthy controls and from each other at each time point, but approached healthy controls over time. Unsupervised feature importance score analysis identified activated T cells, cytotoxic memory and effector T cells [higher in HIV(+)], and naïve and memory T helper cells [lower HIV(+)] as a having a significant impact on differences between HIV(+) AHCT recipient and healthy control lymphocyte composition (p<0.0033). HIV(+) AHCT recipients also demonstrated lower median absolute numbers of activated B cells and lower NK cell sub-populations, compared to healthy controls (p<0.0033) and HIV(-) AHCT recipients (p<0.006). HIV(+) patient T cells showed robust IFNγ production in response to HIV and EBV recall antigens. Overall, HIV(+) AHCT recipients, but not HIV(-) AHCT recipients, exhibited reconstitution of pro-inflammatory immune profiling that was consistent with that seen in patients with chronic HIV infection treated with antiretroviral regimens. Our results further support the use of AHCT in HIV(+) individuals with relapsed/refractory lymphoma.
我们报告了首例对接受自体造血细胞移植(AHCT)的 HIV 相关淋巴瘤患者(n=37,淋巴瘤,BEAM 预处理)、HIV(-)AHCT 患者(n=30,骨髓瘤,马法兰预处理)在 AHCT 后 56、180 和 365 天以及 71 名健康对照者的免疫重建进行的深入比较。主成分分析表明,HIV(+)和 HIV(-)AHCT 受者的免疫细胞组成在每个时间点都远离健康对照者,彼此聚类,但随着时间的推移逐渐接近健康对照者。无监督特征重要性评分分析确定了活化 T 细胞、细胞毒性记忆和效应 T 细胞[在 HIV(+)中更高]以及幼稚和记忆 T 辅助细胞[在 HIV(+)中更低]对 HIV(+)AHCT 受者和健康对照者淋巴细胞组成差异有显著影响(p<0.0033)。与健康对照者(p<0.0033)和 HIV(-)AHCT 受者(p<0.006)相比,HIV(+)AHCT 受者也表现出活化 B 细胞和 NK 细胞亚群的中位数绝对数量较低。与健康对照者相比,HIV(+)患者的 T 细胞对 HIV 和 EBV 回忆抗原表现出强烈的 IFNγ产生。总体而言,HIV(+)AHCT 受者,但不是 HIV(-)AHCT 受者,表现出促炎免疫谱的重建,与接受抗逆转录病毒治疗方案治疗的慢性 HIV 感染患者相似。我们的研究结果进一步支持在复发/难治性淋巴瘤的 HIV(+)个体中使用 AHCT。