Li Xiaoping, Xue Dan, Wei Qiongying, Tan Xuexue
Department of Respiratory and Critical Care Medicine, Fujian Medical University Union Hospital, China.
Department of Respiratory and Critical Care Medicine, Fujian Medical University Union Hospital, China.
Immunobiology. 2025 Jan;230(1):152866. doi: 10.1016/j.imbio.2024.152866. Epub 2025 Jan 5.
Tumor immunotherapy, particularly immune checkpoint inhibitors (ICIs), has emerged as a powerful strategy in treating malignant tumors, exhibiting efficacy in both first-line and second-line treatments for advanced non-small cell lung cancer (NSCLC). Despite their success, ICIs can lead to adverse reactions, including interstitial lung disease (ILD), with an incidence ranging from 2.7 % to 20.0 %. The lack of clear correlations with dosage, duration, or drug efficacy, coupled with nonspecific clinical manifestations, poses challenges in timely diagnosis and effective management. This study examined the association between ICIs-related ILD and serum levels of KL-6 and inflammatory markers in NSCLC patients. A total of 382 NSCLC patients with squamous cell carcinoma (SQC, n = 81), adenocarcinoma (ACA, n = 132), and large cell carcinoma (LCC, n = 169) were included, of whom 191 developed ILD following ICIs treatment. Serum KL-6, TNF-α, IL-8, and IL-6 were quantified using ELISA. Results showed significantly elevated serum KL-6 levels in ILD patients (759.35 ± 214.14 U/mL) compared to those without ILD (270.81 ± 124.98 U/mL). Cancer subtype analysis revealed increased KL-6 levels across SQC, ACA, and LCC ILD patients (SQC: 645.89 ± 255.07, ACA: 797.39 ± 192.30, LCC: 783.57 ± 191.21; p < 0.001). ROC analysis identified diagnostic thresholds for KL-6: 277.4 U/mL for SQC (sensitivity 0.9756, specificity 0.8250), 346.9 U/mL for ACA (sensitivity 0.9583, specificity 0.8333), and 281.3 U/mL for LCC (sensitivity 0.9873, specificity 0.6111). Correlation analysis showed a significant relationship between KL-6 and TNF-α (r = 0.4626, p = 0.0023), IL-8 (r = 0.5584, p = 0.0001), and IL-6 (r = 0.5336, p = 0.0003) in SQC ILD patients. These findings suggest that elevated KL-6 levels and inflammatory markers are indicative of ILD in ICIs-treated NSCLC patients, with potential diagnostic implications across cancer subtypes.
肿瘤免疫疗法，尤其是免疫检查点抑制剂（ICI），已成为治疗恶性肿瘤的有力策略，在晚期非小细胞肺癌（NSCLC）的一线和二线治疗中均显示出疗效。尽管取得了成功，但ICI可导致不良反应，包括间质性肺病（ILD），发病率在2.7%至20.0%之间。由于与剂量、疗程或药物疗效缺乏明确关联，加上临床表现不具特异性，给及时诊断和有效管理带来了挑战。本研究探讨了ICI相关ILD与NSCLC患者血清KL-6水平及炎症标志物之间的关联。共纳入382例NSCLC患者，其中鳞状细胞癌（SQC，n = 81）、腺癌（ACA，n = 132）和大细胞癌（LCC，n = 169），其中191例在ICI治疗后发生ILD。采用酶联免疫吸附测定法（ELISA）对血清KL-6、肿瘤坏死因子-α（TNF-α）、白细胞介素-8（IL-8）和白细胞介素-6（IL-6）进行定量分析。结果显示，与未发生ILD的患者（270.81±124.98 U/mL）相比，ILD患者血清KL-6水平显著升高（759.35±214.14 U/mL）。癌症亚型分析显示，SQC、ACA和LCC的ILD患者KL-6水平均升高（SQC：645.89±255.07，ACA：797.39±192.30，LCC：
