Joao Gorgulho, Timo Trenkner, Eva Kinkel, Britta Fritzsche, Paul Kachel, Sven Peine, Urte Matschl, Markus Altfeld, Samuel Huber, Ansgar W Lohse, Winfried Alsdorf, Carsten Bokemeyer, Angelique Hoelzemer, Wilfredo Garcia Beltran, Johann von Felden
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Levels of sCD27, sCD28, and sCD80 were measured using multiplex immunoassay in 100 lymphoma patients and 62 healthy donors (HD). Expression of membrane-bound isoforms on PBMCs was analyzed via flow cytometry in 40 patients and 10 HD. All three sICs were significantly higher in lymphoma patients compared to HD. High levels were associated with significantly impaired disease control (DC) and survival at 12 and 24 months, progression free-survival (PFS) and overall survival (OS). The highest prediction capacity was achieved when assessing all three molecules in a combined score (p<sub>PFS</sub> < 0.001, p<sub>OS</sub> = 0.013, for score 0 vs 3: DC<sub>12mo</sub>:85% vs 18.5%, OS<sub>24mo</sub>:87% vs 27%). Integrating expression of related membrane-bound markers on PBMCs led to a highly robust peripheral blood-based biomarker score comprising the soluble and membrane-bound compartments (2COMPIC-Score:3 sICs + 7 PBMC subsets) (p<sub>PFS</sub> < 0.001, HR<sub>PFS</sub> = 18.1;p<sub>OS</sub> = 0.001,HR<sub>OS</sub> = 19.2), corroborated by multivariate analysis, outperforming the clinically validated NCCN-IPI prognostic score. We unveil the potential of combining different minimally invasive liquid biopsy-based immune checkpoint assessments into a robust clinical score for prognostic prediction in lymphoma, mainly B(cell)-NHL. 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引用次数: 0
摘要
淋巴瘤，特别是侵袭性非霍奇金淋巴瘤（NHL），由于初始治疗失败的一部分患者预后不佳，仍然具有挑战性。目前用于风险分层的微创生物标志物需要进一步改进。免疫检查点抑制剂（ICIs）虽然在NHL中的疗效有限，但却突出了免疫系统在癌症控制中的关键作用。本研究探讨了可溶性免疫检查点（sICs）及其膜结合异构体在淋巴瘤患者外周血中的预测和预后潜力。在100名淋巴瘤患者和62名健康供者（HD）中使用多重免疫分析法测量sCD27、sCD28和sCD80的水平。通过流式细胞术分析40例患者和10例HD患者PBMCs上膜结合亚型的表达。与HD患者相比，淋巴瘤患者的这三种sic均显著升高。高水平与疾病控制（DC）、12个月和24个月生存率、无进展生存期（PFS）和总生存期（OS）显著受损相关。当评估所有三种分子的综合评分时，达到了最高的预测能力（pPFS OS = 0.013，评分0 vs 3； DC12mo:85% vs 18.5%, OS24mo:87% vs 27%）。整合相关膜结合标志物在PBMC上的表达导致了一个高度稳健的外周血生物标志物评分，包括可溶性和膜结合区室（2COMPIC-Score:3 sICs + 7 PBMC亚群）（pPFS PFS = 18.1;pOS = 0.001,HROS = 19.2），多变量分析证实了这一点，优于临床验证的NCCN-IPI预后评分。我们揭示了将不同的微创液体活检免疫检查点评估结合成淋巴瘤（主要是B（细胞）-NHL）预后预测的强大临床评分的潜力。等待前瞻性验证，我们的发现可以帮助临床医生指导治疗决策。
A dual compartment peripheral blood signature of soluble and membrane-bound immune checkpoints predicts outcome in lymphoma patients.
Lymphomas, particularly aggressive non-Hodgkin lymphomas (NHL), remain challenging due to poor outcomes in a subset of patients who fail initial therapy. Current minimally invasive biomarkers for risk stratification need further improvement. Immune checkpoint inhibitors (ICIs), while with limited efficacy in NHL, highlight the immune system's crucial role in cancer control. This study investigated the predictive and prognostic potential of soluble immune checkpoints (sICs) and their membrane-bound isoforms in the peripheral blood of lymphoma patients. Levels of sCD27, sCD28, and sCD80 were measured using multiplex immunoassay in 100 lymphoma patients and 62 healthy donors (HD). Expression of membrane-bound isoforms on PBMCs was analyzed via flow cytometry in 40 patients and 10 HD. All three sICs were significantly higher in lymphoma patients compared to HD. High levels were associated with significantly impaired disease control (DC) and survival at 12 and 24 months, progression free-survival (PFS) and overall survival (OS). The highest prediction capacity was achieved when assessing all three molecules in a combined score (pPFS < 0.001, pOS = 0.013, for score 0 vs 3: DC12mo:85% vs 18.5%, OS24mo:87% vs 27%). Integrating expression of related membrane-bound markers on PBMCs led to a highly robust peripheral blood-based biomarker score comprising the soluble and membrane-bound compartments (2COMPIC-Score:3 sICs + 7 PBMC subsets) (pPFS < 0.001, HRPFS = 18.1;pOS = 0.001,HROS = 19.2), corroborated by multivariate analysis, outperforming the clinically validated NCCN-IPI prognostic score. We unveil the potential of combining different minimally invasive liquid biopsy-based immune checkpoint assessments into a robust clinical score for prognostic prediction in lymphoma, mainly B(cell)-NHL. Pending prospective validation, our findings could aid clinicians in guiding therapeutic decisions.
期刊介绍：
OncoImmunology is a dynamic, high-profile, open access journal that comprehensively covers tumor immunology and immunotherapy.
As cancer immunotherapy advances, OncoImmunology is committed to publishing top-tier research encompassing all facets of basic and applied tumor immunology.
The journal covers a wide range of topics, including:
-Basic and translational studies in immunology of both solid and hematological malignancies
-Inflammation, innate and acquired immune responses against cancer
-Mechanisms of cancer immunoediting and immune evasion
-Modern immunotherapies, including immunomodulators, immune checkpoint inhibitors, T-cell, NK-cell, and macrophage engagers, and CAR T cells
-Immunological effects of conventional anticancer therapies.
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