Division of Oncology and Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, P.R. China.
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P.R. China.
Animal Model Exp Med. 2023 Oct;6(5):464-473. doi: 10.1002/ame2.12355. Epub 2023 Oct 18.
Immunotherapy has become the fastest-adopting treatment paradigm for lung cancer with improved survival. By binding with its ligand (inducible T-cell co-stimulator and its ligand [ICOSL]), an inducible T-cell co-stimulator (ICOS) could contribute to reversing immunosuppression and improving immune response and thus be a potential target for cancer immunotherapy.
We selected 54 formalin-fixed, paraffin-embedded tumor tissues from cases with stage I-III lung adenocarcinoma cancer. Immunohistochemical expression of ICOS and ICOSL was evaluated. The correlation with clinical parameters in Chinese patients was also compared with TCGA results.
The positive rates of ICOS and ICOSL were 68% and 81.5%, respectively, in lung tumor tissues. Of these, 9 cases had a low expression of ICOS, and 22 cases had a high expression of ICOS; ICOSL expression was low in 20 cases and high in 24 cases. According to the International Association for the Study of Lung Cancer (8th edition), phase I lesions were detected in 21 cases, phase II lesions in 15 cases, and phase III lesions in 18 cases. The median survival time of all patients was 44.5 months, and the median disease-free survival was 32 months. Univariate analysis showed that the factors significantly associated with overall survival were tumor size, regional lymph node involvement, stage, and expression level of ICOS/ICOSL. Survival analysis using log-rank test indicated that the lower ICOS+ cell infiltration may predict poor prognosis, whereas lower ICOSL protein expression may be associated with better prognosis, but ICOSL data need further validation in larger samples due to inconsistency in TCGA mRNA prediction.
ICOS/ICOSL might be associated with prognosis of lung cancer, and ICOS and its ligand may be potential therapeutic targets in non-small cell lung cancer.
免疫疗法已成为改善生存的肺癌最快采用的治疗模式。通过与其配体(诱导型 T 细胞共刺激分子及其配体[ICOSL])结合,诱导型 T 细胞共刺激分子(ICOS)有助于逆转免疫抑制,改善免疫反应,因此可能成为癌症免疫治疗的潜在靶点。
我们从 I 期-III 期肺腺癌患者中选择了 54 例福尔马林固定、石蜡包埋的肿瘤组织。评估了 ICOS 和 ICOSL 的免疫组织化学表达,并与中国患者的临床参数进行了比较,还与 TCGA 结果进行了比较。
在肺肿瘤组织中,ICOS 和 ICOSL 的阳性率分别为 68%和 81.5%。其中,9 例 ICOS 低表达,22 例 ICOS 高表达;20 例 ICOSL 低表达,24 例 ICOSL 高表达。根据国际肺癌研究协会(第 8 版),21 例为 I 期病变,15 例为 II 期病变,18 例为 III 期病变。所有患者的中位总生存期为 44.5 个月,中位无病生存期为 32 个月。单因素分析显示,与总生存期显著相关的因素有肿瘤大小、区域淋巴结受累、分期和 ICOS/ICOSL 的表达水平。采用对数秩检验的生存分析表明,较低的 ICOS+细胞浸润可能预示着不良预后,而较低的 ICOSL 蛋白表达可能与较好的预后相关,但由于 TCGA mRNA 预测不一致,ICOSL 数据需要在更大的样本中进一步验证。
ICOS/ICOSL 可能与肺癌的预后相关,ICOS 及其配体可能是非小细胞肺癌的潜在治疗靶点。