CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：CD161⁺ NKT Cell Proportion as a Predictive Biomarker for Bortezomib Treatment Response in Newly Diagnosed Multiple Myeloma Patients.
CD161⁺ NKT Cell Proportion as a Predictive Biomarker for Bortezomib Treatment Response in Newly Diagnosed Multiple Myeloma Patients.
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外周血 CD3⁺CD56⁺CD161⁺ NKT 细胞低表达与 NDMM 中肿瘤负荷增加和硼替佐米耐药相关，提示其有潜力作为治疗反应的预测性生物标志物。
多发性骨髓瘤（MM）仍不可治愈，耐药是其关键临床挑战。自然杀伤T（NKT）细胞功能受损可能促进MM免疫逃逸，而NKT细胞上抑制性受体CD161表达的意义尚不明确。本研究探讨了新诊断MM（NDMM）患者外周血CD3⁺CD56⁺CD161⁺ NKT细胞比例与硼替佐米联合地塞米松治疗反应之间的关联。
纳入72例接受硼替佐米联合地塞米松治疗的NDMM患者和37例健康对照（HCs）。采用流式细胞术检测治疗前后外周血CD3⁺CD56⁺CD161⁺细胞比例。根据IMWG标准评估治疗反应（缓解者：≥部分缓解[PR]；未缓解者：≤疾病稳定[SD]）。采用受试者工作特征（ROC）曲线分析评估预测价值。分析其与临床参数（ISS分期、LDH、β₂-MG等）的相关性。
NDMM患者基线CD3⁺CD56⁺CD161⁺比例显著低于HCs（2.25% vs. 4.20%，p < 0.05）。治疗后，该比例升高至3.10%（p < 0.05）。缓解者的基线比例显著高于未缓解者（3.40% vs. 1.60%，p < 0.0001）。ROC分析显示，基线比例可预测治疗反应，AUC为0.789（95% CI：0.675 - 0.903）。在最佳截断值1.85%时，敏感性为87.9%，特异性为71.8%。比例较低（< 1.85%）的患者ISS III期发生率更高（p < 0.05），且LDH和β₂-MG水平显著升高（均p < 0.05）。
Multiple myeloma (MM) remains incurable, with drug resistance being a key clinical challenge. Impaired natural killer T (NKT) cell function may contribute to MM immune escape, while the significance of the inhibitory receptor CD161 expression on NKT cells is unclear. This study investigated the association between the peripheral blood CD3⁺CD56⁺CD161⁺ NKT cell proportion and response to bortezomib plus dexamethasone therapy in newly diagnosed MM (NDMM) patients.
Seventy-two NDMM patients receiving bortezomib plus dexamethasone and 37 healthy controls (HCs) were enrolled. Flow cytometry assessed the peripheral blood CD3⁺CD56⁺CD161⁺ cell proportion before and after treatment. Treatment response was evaluated according to IMWG criteria (responders: ≥ partial response [PR]; non-responders: ≤ stable disease [SD]). Receiver operating characteristic (ROC) curve analysis evaluated predictive value. Correlation with clinical parameters (ISS stage, LDH, β₂-MG, etc.) was analyzed.
The baseline CD3⁺CD56⁺CD161⁺ proportion was significantly lower in NDMM patients than in HCs (2.25% vs. 4.20%, p < 0.05). After treatment, it increased to 3.10% (p < 0.05). Responders had a significantly higher baseline proportion than non-responders (3.40% vs. 1.60%, p < 0.0001). ROC analysis showed the baseline proportion predicted treatment response with an AUC of 0.789 (95% CI: 0.675 - 0.903). At the optimal cutoff of 1.85%, sensitivity was 87.9% and specificity was 71.8%. Patients with low proportions (< 1.85%) had a higher frequency of ISS stage III (p < 0.05) and significantly elevated LDH and β₂-MG levels (both p < 0.05).
Low expression of peripheral blood CD3⁺CD56⁺CD161⁺ NKT cells is associated with increased tumor burden and bortezomib resistance in NDMM, suggesting its potential as a predictive biomarker for treatment response.
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