Department of Pharmacy, Medical Supplies Center of Chinese PLA General Hospital, Beijing, China.
Department of Clinical Laboratory, The First Medical Center of Chinese PLA General Hospital, Beijing, China.
Front Immunol. 2024 Oct 10;15:1458488. doi: 10.3389/fimmu.2024.1458488. eCollection 2024.
Hematological indicators in the early stage of PD-1 inhibitor treatment may show superior predictive ability of the occurrence of immune related adverse event (irAE) compared to the pre-treatment indicators, as the immune response is modulated during the PD-1 inhibitor treatment. The objective of this study was to investigate the predictive capabilities of biomarkers in the early treatment stage for immune related thyroid dysfunction (irTD), and explore the potential predictive cytokines.
Medical records and blood test results of cancer patients treated with PD-1 inhibitor at a certain medical institution were collected. Logistic regression analysis was utilized to identify the predictive factors of irTD, ROC curves were plotted and the area under the curves (AUC) was calculated. Serum samples were collected before and during early treatment phase, cytokine detection was performed to explore potential predictive cytokines.
A total of 264 patients were enrolled, 58 developed irTD (21.97%), including 31 patients with thyrotoxicosis and 27 with hypothyroidism. There were no significant differences in demographic characteristics, tumor types and PD-1 inhibitors between patients with and without irTD. Multivariate logistic analysis showed that anti-thyroglobulin antibody (TgAb) (OR=2.831, 95%CI: 1.077-7.443, =0.035) and anti-thyroperoxidase antibody (TPOAb) (OR=9.565, 95%CI: 3.399-26.921, =0.000) in the early treatment phase were independent predictive factors for irTD, the AUC of early-stage biomarkers was larger than that of pre-treatment (0.655 vs 0.571); low level of TSH at the early stage (OR=0.162, 95%CI: 0.077-0.341, =0.000) was significantly correlated with thyrotoxicosis; female (OR=3.889, 95%CI: 1.457-10.380, =0.007) and positive TPOAb (OR=8.678, 95%CI: 2.656-28.357, =0.000) at the early stage were significantly correlated with hypothyroidism. The AUCs of early-stage biomarkers were larger than that of pre-treatment both in thyrotoxicosis (0.812 vs 0.637) and hypothyroidism patients (0.728 vs 0.710). The increase of IL-16 (adjusted =0.004), IL-12p70 (adjusted =0.014), IL-17 (adjusted =0.014), CCL-15 (adjusted =0.014) and IL-1a (adjusted =0.021) in the early treatment phase were positively correlated with irTD.
Biomarkers at the early stage of PD-1 inhibitor treatment could predict irTD, and demonstrated stronger predictive ability compared to pre-treatment biomarkers. IL-16, IL-12p70, IL-17, CCL-15 and IL-1a could serve as potential predictive biomarkers for irTD.
与治疗前指标相比，PD-1 抑制剂治疗早期的血液学指标可能对免疫相关不良事件（irAE）的发生具有更好的预测能力，因为免疫反应在 PD-1 抑制剂治疗期间被调节。本研究旨在探讨早期治疗阶段生物标志物对免疫相关甲状腺功能障碍（irTD）的预测能力，并探索潜在的预测细胞因子。
收集某医疗机构接受 PD-1 抑制剂治疗的癌症患者的病历和血液检查结果。采用逻辑回归分析识别 irTD 的预测因素，绘制 ROC 曲线并计算曲线下面积（AUC）。在早期治疗阶段采集血清样本，进行细胞因子检测，以探索潜在的预测性细胞因子。
共纳入 264 例患者，58 例发生 irTD（21.97%），其中 31 例为甲状腺毒症，27 例为甲状腺功能减退症。irTD 患者与无 irTD 患者在人口统计学特征、肿瘤类型和 PD-1 抑制剂方面无显著差异。多变量逻辑分析显示，早期治疗阶段的抗甲状腺球蛋白抗体（TgAb）（OR=2.831，95%CI：1.077-7.443，=0.035）和抗甲状腺过氧化物酶抗体（TPOAb）（OR=9.565，95%CI：3.399-26.921，=0.000）是 irTD 的独立预测因素，早期阶段生物标志物的 AUC 大于治疗前（0.655 比 0.571）；早期阶段 TSH 水平较低（OR=0.162，95%CI：0.077-0.341，=0.000）与甲状腺毒症显著相关；女性（OR=3.889，95%CI：1.457-10.380，=0.007）和早期 TPOAb 阳性（OR=8.678，95%CI：2.656-28.357，=0.000）与甲状腺功能减退症显著相关。在甲状腺毒症（0.812 比 0.637）和甲状腺功能减退症患者（0.728 比 0.710）中，早期阶段生物标志物的 AUC 均大于治疗前。在早期治疗阶段，IL-16（调整后=0.004）、IL-12p70（调整后=0.014）、IL-17（调整后=0.014）、CCL-15（调整后=0.014）和 IL-1a（调整后=0.021）的增加与 irTD 呈正相关。
PD-1 抑制剂治疗早期的生物标志物可预测 irTD，与治疗前的生物标志物相比，具有更强的预测能力。IL-16、IL-12p70、IL-17、CCL-15 和 IL-1a 可作为 irTD 的潜在预测生物标志物。
