Department of Clinical Laboratory, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China.
Department of Experimental Research, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou 510060, P. R. China.
J Immunother Cancer. 2023 Aug;11(8). doi: 10.1136/jitc-2022-006552.
Immune checkpoint inhibitors (ICIs)-based treatments have been recommended as the first line for refractory recurrent and/or metastatic nasopharyngeal carcinoma (NPC) patients, yet responses vary, and predictive biomarkers are urgently needed. We selected serum interleukin-15 (sIL-15) out of four interleukins as a candidate biomarker, while most patients' sIL-15 levels were too low to be detected by conventional methods, so it was necessary to construct a highly sensitive method to detect sIL-15 in order to select NPC patients who would benefit most or least from ICIs.
Combining a primer exchange reaction (PER), transcription-mediated amplification (TMA), and a immuno-PER-TMA-CRISPR/Cas13a system, we developed a novel multiple signal amplification platform with a detection limit of 32 fg/mL, making it 153-fold more sensitive than ELISA.
This platform demonstrated high specificity, repeatability, and versatility. When applied to two independent cohorts of 130 NPC sera, the predictive value of sIL-15 was accurate in both cohorts (area under the curve: training, 0.882; validation, 0.898). Additionally, lower sIL-15 levels were correlated with poorer progression-free survival (training, HR: 0.080, p<0.0001; validation, HR: 0.053, p<0.0001).
This work proposes a simple and sensitive approach for sIL-15 detection to provide insights for personalized immunotherapy of NPC patients.
免疫检查点抑制剂（ICI）治疗已被推荐为复发性和/或转移性鼻咽癌（NPC）患者的一线治疗方法，但应答情况各不相同，因此迫切需要预测生物标志物。我们从四种白细胞介素中选择血清白细胞介素-15（sIL-15）作为候选生物标志物，然而大多数患者的 sIL-15 水平太低，常规方法无法检测到，因此需要构建一种高灵敏度的方法来检测 sIL-15，以便选择最有可能或最不可能从 ICI 中获益的 NPC 患者。
我们结合引物交换反应（PER）、转录介导扩增（TMA）和免疫 PER-TMA-CRISPR/Cas13a 系统，开发了一种新型的多信号放大平台，检测限为 32 fg/mL，比 ELISA 灵敏 153 倍。
该平台具有高特异性、可重复性和多功能性。当应用于两个独立的 130 例 NPC 血清队列时，sIL-15 的预测价值在两个队列中都很准确（训练队列，AUC：0.882；验证队列，AUC：0.898）。此外，较低的 sIL-15 水平与无进展生存期较差相关（训练队列，HR：0.080，p<0.0001；验证队列，HR：0.053，p<0.0001）。
本研究提出了一种简单灵敏的 sIL-15 检测方法，为 NPC 患者的个体化免疫治疗提供了思路。
