免疫检查点抑制剂（ICIs）治疗已被推荐作为难治性复发和/或转移性鼻咽癌（NPC）患者的一线治疗方法，然而，患者的反应存在差异，迫切需要预测性生物标志物。我们从四种白细胞介素中选择了血清白细胞介素-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，以至于无法通过常规方法检测到，因此需要构建一种高灵敏度的方法来检测sIL-15，以选择能够从ICIs中获益最多或最少的NPC患者。通过结合引物交换反应（PER）、转录介导扩增（TMA）和免疫- PER- TMA- CRISPR/Cas13a系统，我们开发了一种新型的多信号放大平台，检测限度为32 fg/mL，比ELISA灵敏度高153倍。这种平台具有高特异性、重复性和通用性。当应用于两个独立的130个NPC血清队列时，sIL-15的预测价值在两个队列中都准确（曲线下面积：训练，0.882；验证，0.898）。此外，较低的sIL-15水平与较差的无进展生存相关（训练，HR：0.080，p<0.0001；验证，HR：0.053，p<0.0001）。本研究提出了一种简单且灵敏的sIL-15检测方法，为NPC患者的个体化免疫治疗提供了新的见解。© 作者（或其雇主）2023年授权再使用CC BY-NC。不得进行商业再利用。详见权益和权限。由BMJ出版。

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.© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.