免疫检查点治疗和响应生物标志物在非小细胞肺癌中：血清NY-ESO-1和XAGE1抗体作为预测和监测标志物。
Immune checkpoint therapy and response biomarkers in non-small-cell lung cancer: Serum NY-ESO-1 and XAGE1 antibody as predictive and monitoring markers.
发表日期：2023
作者：
Koji Kurose, Kanako Sakaeda, Minoru Fukuda, Yumiko Sakai, Hiroyuki Yamaguchi, Shinnosuke Takemoto, Katsuhiko Shimizu, Takeshi Masuda, Katsumi Nakatomi, Shigeo Kawase, Ryo Tanaka, Takayuki Suetsugu, Keiko Mizuno, Takehiro Hasegawa, Yusuke Atarashi, Yasuhiro Irino, Toshiyuki Sato, Hiromasa Inoue, Noboru Hattori, Eiichiro Kanda, Masao Nakata, Hiroshi Mukae, Toru Oga, Mikio Oka
来源：
Advances in Clinical Chemistry
摘要：
免疫检查点抑制剂（ICI）是晚期非小细胞肺癌（NSCLC）全身治疗的关键药物，并最近被纳入新辅助和辅助手术切除治疗中。目前，ICI联合细胞毒药物在临床实践中被广泛使用，但是一些ICI临床试验未能产生长期临床效益。不幸的是，考虑到身体和财务负担，临床效益是适度和有限的。因此，选择适合的患者和ICI治疗方案很重要，而生物标志物对于选择这些患者是必要的。肿瘤PD-L1表达被普遍用作生物标志物，然而，由于病理学家的视觉评分系统，PD-L1测定显示低分析有效性和重复性。最近的肿瘤免疫学研究表明，源自体细胞突变的新抗原和T和B细胞之间的协作有效地引发抗肿瘤反应。这表明，高肿瘤突变负担和T细胞浸润是预测生物标志物。然而，产生抗体（Ab）的B细胞仍然是生物标志物了解和分析不足的。我们发现，癌胚抗原的NY-ESO-1和XAGE1经常引发NSCLC中自发的体液和细胞免疫反应。约25％的NSCLC患者检测到这些抗原的血清抗体，并预测ICI单药疗法的反应。此外，在ICI治疗后随着肿瘤收缩，抗体水平也会降低。因此，NY-ESO-1和XAGE1 Ab可能是预测和监测ICI治疗反应的生物标志物。对于临床应用，开发了完全自动化的测量抗体的分析系统。在这里，我们回顾了当前的ICI治疗，肿瘤免疫学和NSCLC中的生物标志物，并讨论了血清生物标志物NY-ESO-1和XAGE1 Ab的适用性。Copyright © 2023 Elsevier Inc. All rights reserved.
Immune checkpoint inhibitors (ICI) are key drugs in systemic therapy for advanced non-small-cell lung cancer (NSCLC) and have recently been incorporated into neoadjuvant and adjuvant settings for surgical resection. Currently, ICI combinations with cytotoxic agents are frequently used in clinical practice, although several ICI clinical trials have failed to produce long-term clinical benefits. Unfortunately, clinical benefit is moderate and limited considering physical and financial burden. Therefore, selecting appropriate patients and regimens for ICI therapy is important, and biomarkers are necessary for their selection. Tumor PD-L1 expression is universally used as a biomarker; however, PD-L1 assays show low analytical validity and reproducibility due to the visual-scoring system by pathologists. Recent tumor immunology studies explore that neoantigens derived from somatic mutations and the collaboration between T and B cells efficiently elicit antitumor responses. This suggests that high tumor mutational burden and T-cell infiltration are predictive biomarkers. However, B cells producing antibody (Ab) remain poorly understood and analyzed as biomarkers. We found that NY-ESO-1 and XAGE1 of cancer-testis antigen frequently elicit spontaneous humoral and cellular immune responses in NSCLC. Serum Ab against these antigens were detected in approximately 25% of NSCLC patients and predicted ICI monotherapy responses. In addition, the Ab levels were decreased with tumor shrinkage after ICI therapy. Thus, NY-ESO-1 and XAGE1 Ab are potentially biomarkers predicting and monitoring response to ICI therapy. For clinical applications, a fully-automated assay system measuring the Ab was developed. Here, we review current ICI therapy, tumor immunology, and biomarkers in NSCLC, and discuss the applicability of the serum biomarkers NY-ESO-1 and XAGE1 Ab.Copyright © 2023 Elsevier Inc. All rights reserved.