Assessing the prognosis of patients with aggressive non-Hodgkin B cell lymphoma mainly relies on a clinical risk score (IPI). Standard first-line therapies are based on a chemo-immunotherapy with rituximab, which mediates CD16-dependent antibody-dependent cellular cytotoxicity (ADCC). We phenotypically and functionally analyzed blood samples from 46 patients focusing on CD16+ NK cells, CD16+ T cells and CD16+ monocytes. Kaplan-Meier survival curves show a superior progression-free survival (PFS) for patients having more than 1.6% CD16+ T cells (p = 0.02; HR = 0.13 (0.007–0.67)) but an inferior PFS having more than 10.0% CD16+ monocytes (p = 0.0003; HR = 16.0 (3.1-291.9)) at diagnosis. Surprisingly, no correlation with NK cells was found. The increased risk of relapse in the presence of > 10.0% CD16+ monocytes is reversed by the simultaneous occurrence of > 1.6% CD16+ T cells. The unexpectedly strong protective function of CD16+ T cells could be explained by their high antibody-dependent cellular cytotoxicity as quantified by real-time killing assays and single-cell imaging. The combined analysis of CD16+ monocytes (> 10%) and CD16+ T cells (< 1.6%) provided a strong model with a Harrell’s C index of 0.80 and a very strong power of 0.996 even with our sample size of 46 patients. CD16 assessment in the initial blood analysis is thus a precise marker for early relapse prediction. High CD16+ T cell counts have a positive correlation with PFS in aggressive NHL/DLBCL patients (p = 0.02; HR = 0.13, 0.01–0.7). High CD16+ monocyte counts have a negative correlation with PFS in aggressive NHL/DLBCL patients (p = 0.0003; HR = 16.0, 3-292). The combined assessment of CD16+ T cells and CD16+ monocytes accurately predicts PFS in aggressive NHL/DLBCL patients. The strong protective function of CD16+ T cells could be explained by their high antibody-dependent cellular cytotoxicity.

中文翻译：

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CD16+ 作为侵袭性 B-NHL/DLBCL 患者早期复发的预测标志物


评估侵袭性非霍奇金 B 细胞淋巴瘤患者的预后主要依靠临床风险评分 (IPI)。标准一线疗法基于利妥昔单抗化学免疫疗法，其介导 CD16 依赖性抗体依赖性细胞毒性 (ADCC)。我们对 46 名患者的血液样本进行了表型和功能分析，重点分析了 CD16+ NK 细胞、CD16+ T 细胞和 CD16+ 单核细胞。 Kaplan-Meier 生存曲线显示，CD16+ T 细胞超过 1.6% 的患者无进展生存期 (PFS) 较高（p = 0.02；HR = 0.13 (0.007–0.67)），但 CD16+ 单核细胞超过 10.0% 的患者 PFS 较差诊断时（p = 0.0003；HR = 16.0 (3.1-291.9)）。令人惊讶的是，没有发现与 NK 细胞的相关性。 > 10.0% CD16+ 单核细胞存在时复发风险的增加可通过同时出现 > 1.6% CD16+ T 细胞来逆转。 CD16+ T 细胞出人意料的强大保护功能可以通过其高抗体依赖性细胞毒性来解释，通过实时杀伤测定和单细胞成像进行量化。 CD16+ 单核细胞 (> 10%) 和 CD16+ T 细胞 (< 1.6%) 的组合分析提供了一个强大的模型，Harrell's C 指数为 0.80，即使我们的样本量为 46 名患者，功效也非常强，为 0.996。因此，初始血液分析中的 CD16 评估是早期复发预测的精确标记。高 CD16+ T 细胞计数与侵袭性 NHL/DLBCL 患者的 PFS 呈正相关（p = 0.02；HR = 0.13、0.01–0.7）。高 CD16+ 单核细胞计数与侵袭性 NHL/DLBCL 患者的 PFS 呈负相关（p = 0.0003；HR = 16.0, 3-292）。 CD16+ T 细胞和 CD16+ 单核细胞的联合评估可准确预测侵袭性 NHL/DLBCL 患者的 PFS。 CD16+ T 细胞的强保护功能可以通过其高抗体依赖性细胞毒性来解释。