CD16+ as predictive marker for early relapse in aggressive B-NHL/DLBCL patients

IF 27.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular Cancer Pub Date : 2024-09-28 DOI:10.1186/s12943-024-02123-7

Sylvia Zöphel, Nadja Küchler, Johanna Jansky, Cora Hoxha, Gertrud Schäfer, Julius J. Weise, Joanne Vialle, Lea Kaschek, Gebhard Stopper, Hermann Eichler, Daniela Yildiz, Alina Moter, Philipp Wendel, Evelyn Ullrich, Claudia Schormann, Torben Rixecker, Onur Cetin, Frank Neumann, Patrick Orth, Moritz Bewarder, Markus Hoth, Lorenz Thurner, Eva C. Schwarz

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Abstract

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.

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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）。标准的一线疗法是基于利妥昔单抗的化疗免疫疗法，它能介导 CD16 依赖性抗体依赖性细胞毒性（ADCC）。我们对 46 例患者的血液样本进行了表型和功能分析，重点研究 CD16+ NK 细胞、CD16+ T 细胞和 CD16+ 单核细胞。卡普兰-米尔生存曲线显示，诊断时CD16+ T细胞超过1.6%的患者无进展生存期（PFS）较长（p = 0.02；HR = 0.13 (0.007-0.67)），而CD16+单核细胞超过10.0%的患者无进展生存期较短（p = 0.0003；HR = 16.0 (3.1-291.9)）。令人惊讶的是，该研究并未发现与 NK 细胞的相关性。CD16+ 单核细胞>10.0%时，复发风险增加，而同时CD16+ T细胞>1.6%时，复发风险则会逆转。CD16+ T细胞具有意想不到的强大保护功能，这可以用实时杀伤检测和单细胞成像量化的高抗体依赖性细胞毒性来解释。对 CD16+ 单核细胞（> 10%）和 CD16+ T 细胞（< 1.6%）的联合分析提供了一个强大的模型，哈雷尔 C 指数为 0.80，即使我们的样本量仅为 46 例患者，也能达到 0.996 的极高功率。因此，初次血液分析中的 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）。综合评估 CD16+ T 细胞和 CD16+ 单核细胞可准确预测侵袭性 NHL/DLBCL 患者的 PFS。CD16+ T细胞强大的保护功能可归因于其高度的抗体依赖性细胞毒性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Cancer 医学-生化与分子生物学

CiteScore

54.90

自引率

2.70%

发文量

224

审稿时长

2 months

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