Prognostic significance of NY-ESO-1 antigen and PIGR expression in esophageal tumors of CHP-NY-ESO-1-vaccinated patients as adjuvant therapy.
Prognostic significance of NY-ESO-1 antigen and PIGR expression in esophageal tumors of CHP-NY-ESO-1-vaccinated patients as adjuvant therapy.
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NY-ESO-1 抗原和 PIGR 表达在 CHP-NY-ESO-1 疫苗接种患者的食管肿瘤中作为辅助治疗的预后意义。
DOI：
10.1007/s00262-022-03194-5
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Tetsuya Abe,...Hiroshi Shiku
中科院分区：
文献类型：
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作者：
Yasuhiro Nagata;Shinichi Kageyama;Takeshi Ishikawa;Satoshi Kokura;Tetsuya Okayama;Tetsuya Abe,...Hiroshi Shiku
本研究的目的是确定CHP-NY-ESO-1疫苗与全长NY-ESO-1蛋白和胆固醇酰普鲁兰（CHP）复合物在食管鳞状细胞癌（ESCC）术后患者中的疗效和生物标志物。我们进行了一项随机II期试验。54例表达ny - eso -1的ESCC患者在顺铂/5-氟尿嘧啶为基础的新辅助化疗后接受根治性手术，被分配接受CHP-NY-ESO-1疫苗接种或观察作为对照。6剂CHP-NY-ESO-1每两周皮下注射一次，随后每四周再注射9剂。终点为无病生存期（DFS）和安全性。利用基因表达谱对肿瘤组织进行探索性分析，寻找生物标志物。27例接种疫苗患者未发生严重不良事件，验证了疫苗的安全性。疫苗组和对照组2年DFS分别为56.0%和58.3%。25例患者中24例接种疫苗后出现ny - eso -1特异性IgG应答。对接种疫苗患者的队列内相关性分析显示，NY-ESO-1表达5%或更高是一个有利因素。基因表达谱的综合分析显示，编码聚合免疫球蛋白受体（PIGR）的基因在肿瘤中的表达对接种疫苗队列的预后有显著的有利影响。高pigr表达的肿瘤具有较高的ny - eso -1特异性IgA反应，往往预后良好。这些结果表明，在NY-ESO-1疫苗接种期间，pigr将以抗原特异性的方式在肿瘤免疫中发挥重要作用。IgA反应可能与此有关。
The aim of this study was to determine the efficacy and the biomarkers of the CHP-NY-ESO-1 vaccine complexed with full-length NY-ESO-1 protein and a cholesteryl pullulan (CHP) in patients with esophageal squamous cell carcinoma (ESCC) after surgery. We conducted a randomized phase II trial. Fifty-four patients with NY-ESO-1–expressing ESCC who underwent radical surgery following cisplatin/5-fluorouracil–based neoadjuvant chemotherapy were assigned to receive either CHP-NY-ESO-1 vaccination or observation as control. Six doses of CHP-NY-ESO-1 were administered subcutaneously once every two weeks, followed by nine more doses once every four weeks. The endpoints were disease-free survival (DFS) and safety. Exploratory analysis of tumor tissues using gene-expression profiles was also performed to seek the biomarker. As there were no serious adverse events in 27 vaccinated patients, we verified the safety of the vaccine. DFS in 2 years were 56.0% and 58.3% in the vaccine arm and in the control, respectively. Twenty-four of 25 patients showed NY-ESO-1-specific IgG responses after vaccination. Analysis of intra-cohort correlations among vaccinated patients revealed that 5% or greater expression of NY-ESO-1 was a favorable factor. Comprehensive analysis of gene expression profiles revealed that the expression of the gene encoding polymeric immunoglobulin receptor (PIGR) in tumors had a significantly favorable impact on outcomes in the vaccinated cohort. The highPIGR-expressing tumors that had higher NY-ESO-1-specific IgA response tended to have favorable prognosis. These results suggest thatPIGRwould play a major role in tumor immunity in an antigen-specific manner during NY-ESO-1 vaccinations. The IgA response may be relevant.