Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Affinity Proteomics, SciLifeLab, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH-Royal Institute of Technology, Stockholm, Sweden.
Lung Cancer. 2018 Nov;125:157-163. doi: 10.1016/j.lungcan.2018.09.012. Epub 2018 Sep 17.
Cancer-testis antigens (CTAs) are defined as proteins that are specifically expressed in testis or placenta and their expression is frequently activated in cancer. Due to their ability to induce an immune response, CTAs may serve as suitable targets for immunotherapy. The aim of this study was to evaluate if there is reactivity against CTAs in the plasma of non-small cell lung cancer (NSCLC) patients through the detection of circulating antibodies.
To comprehensively analyze autoantibodies against CTAs the multiplexing capacities of suspension bead array technology was used. Bead arrays were created with 120 protein fragments, representing 112 CTAs. Reactivity profiles were measured in plasma samples from 133 NSCLC patients and 57 cases with benign lung diseases.
Altogether reactivity against 69 antigens, representing 81 CTAs, was demonstrated in at least one of the analyzed samples. Twenty-nine of the antigens (45 CTAs) demonstrated exclusive reactivity in NSCLC samples. Reactivity against cancer-testis antigen family 47; member A (CT47A) genes, P antigen family member 3 (PAGE3), variable charge X-linked (VCX), melanoma antigen family B1 (MAGEB1), lin-28 homolog B (LIN28B) and chromosome 12 open reading frame 54 (C12orf54) were only found in NSCLC patients at a frequency of 1%-4%. The presence of autoantibodies towards these six antigens was confirmed in an independent group of 34 NSCLC patients.
We identified autoantibodies against CTAs in the plasma of lung cancer patients. The reactivity pattern of autoantibodies was higher in cancer patients compared to the benign group, stable over time, but low in frequency of occurrence. The findings suggest that some CTAs are immunogenic and that these properties can be utilized as immune targets.
癌症睾丸抗原(CTAs)被定义为仅在睾丸或胎盘组织中特异性表达且其表达在癌症中常被激活的蛋白。由于它们能够诱导免疫反应,CTAs 可作为免疫治疗的合适靶点。本研究旨在通过检测循环抗体来评估非小细胞肺癌(NSCLC)患者血浆中是否存在针对 CTA 的反应性。
为了全面分析针对 CTA 的自身抗体,采用悬浮珠阵列技术的多重分析能力。用代表 112 个 CTA 的 120 个蛋白片段构建珠阵列。在 133 例 NSCLC 患者和 57 例良性肺部疾病患者的血浆样本中测量反应性图谱。
在至少一个分析样本中,共显示针对 69 个抗原(代表 81 个 CTA)的反应性。29 个抗原(45 个 CTA)在 NSCLC 样本中表现出独特的反应性。对癌症睾丸抗原家族 47;成员 A(CT47A)基因、P 抗原家族成员 3(PAGE3)、可变电荷 X 连锁(VCX)、黑素瘤抗原家族 B1(MAGEB1)、Lin-28 同源物 B(LIN28B)和染色体 12 开放阅读框 54(C12orf54)的自身抗体仅在 NSCLC 患者中以 1%-4%的频率出现。在一个独立的 34 例 NSCLC 患者组中,确认了这些六个抗原的自身抗体的存在。
我们在肺癌患者的血浆中鉴定出针对 CTA 的自身抗体。与良性组相比,癌症患者的自身抗体反应性模式更高,随时间稳定,但发生频率较低。这些发现表明,一些 CTA 具有免疫原性,这些特性可被用作免疫靶标。