Immune complexome analysis of serum samples from non-small-cell lung cancer patients identifies predictive biomarkers for nivolumab therapy
Immune complexome analysis of serum samples from non-small-cell lung cancer patients identifies predictive biomarkers for nivolumab therapy
复制标题
对非小细胞肺癌患者血清样本进行免疫复合体分析，确定纳武单抗治疗的预测生物标志物
DOI：
10.1016/j.cca.2022.05.021
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发表时间：
2022
影响因子：
5
通讯作者：
Ohyama Kaname
中科院分区：
文献类型：
--
作者：
Aizawa Rika;Nakamura Yoichi;Ikeda Takaya;Aibara Nozomi;Kutsuna Yuki J.;Kurosaki Tomoaki;Aki Keisei;Junya Hashizume;Nakagawa Hiroo;Sato Kayoko;Kodama Yukinobu;Nakashima Mihoko N.;Nakashima Mikiro;Mukae Hiroshi;Ohyama Kaname
背景免疫检查点抑制剂（ICI）在癌症治疗中取得了重要成果。然而，目前的临床生物标志物检测并不适合某些患者，因为它们需要肿瘤组织，并且对治疗反应的预测价值很差。因此，识别的生物标志物，使筛选测试在所有patients.MethodsWe进行了nivolumab治疗的非小细胞肺癌患者的免疫复合物组分析，全面识别和比较抗原纳入免疫复合物（IC抗原）的血清样品中的反应者（n = 15）和非反应者（n = 20）。结果治疗前检测到的预测性生物标志物的组合是profilin-1、嘌呤核苷磷酸化酶、α-烯醇化酶和核苷二磷酸激酶A [p = 0.0043，优势比= 2.26，95%置信区间（CI）= 1.19-4.28，曲线下面积= 0.76]。治疗后检测到的预测性生物标志物组合为肽基脯氨酰顺反异构酶A、泛素样修饰物激活酶1、补体成分C8 β链和载脂蛋白L1（p = 0.0039，比值比= 2.56，95% CI = 1.25-5.23，结论血清IC抗原组合可预测纳武单抗治疗非小细胞肺癌的疗效。
BackgroundImmune checkpoint inhibitors (ICIs) have achieved important outcomes in cancer treatment. However, current clinical biomarker tests are not suitable for some patients because they require tumor tissues and have poor predictive value for treatment responses. Therefore, the identification of biomarkers that enable screening tests in all patients is necessary.MethodsWe performed an immune complexome analysis of non-small cell lung cancer patients treated with nivolumab to comprehensively identify and compare antigens incorporated into immune complexes (IC-antigens) in serum samples from the responders (n = 15) and non-responders (n = 20). Additionally, combinations of IC-antigens characteristic to the responder group were evaluated by logistic regression analysis and receiver operating characteristics curves to examine their predictiveness for ICI treatment responses.ResultsThe combination of predictive biomarkers detected before treatment was profilin-1, purine nucleoside phosphorylase, alpha-enolase, and nucleoside diphosphate kinase A [p = 0.0043, odds ratio = 2.26, 95% confidence interval (CI) = 1.19–4.28, area under the curve = 0.76]. The combination of predictive biomarkers detected after treatment was peptidyl-prolyl cis–trans isomerase A, ubiquitin-like modifier-activating enzyme 1, complement component C8 beta chain, and apolipoprotein L1 (p = 0.0039, odds ratio = 2.56, 95% CI = 1.25–5.23, area under the curve = 0.77).ConclusionCombinations of serum IC-antigens may predict the therapeutic effect of nivolumab in non-small cell lung cancer patients.