Maintenance of WT1 expression in tumor cells is associated with a good prognosis in malignant glioma patients treated with WT1 peptide vaccine immunotherapy
Maintenance of WT1 expression in tumor cells is associated with a good prognosis in malignant glioma patients treated with WT1 peptide vaccine immunotherapy
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肿瘤细胞中 WT1 表达的维持与接受 WT1 肽疫苗免疫治疗的恶性胶质瘤患者的良好预后相关
DOI：
10.1007/s00262-021-02954-z
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Hashimoto Naoya
中科院分区：
文献类型：
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作者：
Yokota Chisato;Kagawa Naoki;Takano Koji;Chiba Yasuyoshi;Kinoshita Manabu;Kijima Noriyuki;Oji Yusuke;Oka Yoshihiro;Sugiyama Haruo;Tsuboi Akihiro;Izumoto Shuichi;Kishima Haruhiko;Hashimoto Naoya
我们先前已经揭示了恶性胶质瘤中Wilms肿瘤基因1（WT 1）的过度表达，并开发了WT 1肽疫苗癌症免疫治疗。II期临床试验表明WT 1肽疫苗对复发性恶性胶质瘤的临床疗效。在这里，我们的目的是研究WT 1肽疫苗治疗前后胶质瘤组织中的免疫微环境。配对组织样品获自20名恶性神经胶质瘤患者，所述恶性神经胶质瘤患者已接受WT 1肽疫苗> 3个月并且在疫苗接种期间经历了经放射学和/或临床证实的肿瘤进展。我们发现接种疫苗后肿瘤细胞中WT 1和HLA I类抗原的表达显著降低。在疫苗接种期间，肿瘤细胞中WT 1（免疫治疗的靶分子）表达的维持与较长的无进展生存期和总生存期显著相关。免疫前标本中HLA I类抗原的高表达和低CD 4 +/CD 8+肿瘤浸润淋巴细胞（TIL）比率也与良好的预后相关。接种前和接种后标本之间浸润的CD 3+或CD 8 +T细胞数量无统计学显著差异，而接种后标本中浸润的CD 4 +T细胞数量显著减少。这项研究提供了深入了解WT 1肽疫苗治疗期间肿瘤内免疫反应/逃逸的机制，并为癌症免疫治疗提出了潜在的临床策略。
We have previously revealed the overexpression of Wilms’ tumor gene 1 (WT1) in malignant glioma and developed WT1 peptide vaccine cancer immunotherapy. A phase II clinical trial indicated the clinical efficacy of the WT1 peptide vaccine for recurrent malignant glioma. Here, we aimed to investigate the immunological microenvironment in glioma tissues before and after WT1 peptide vaccine treatment. Paired tissue samples were obtained from 20 malignant glioma patients who had received the WT1 peptide vaccine for > 3 months and experienced tumor progression, confirmed radiographically and/or clinically, during vaccination. We discovered that the expression of WT1 and HLA class I antigens in the tumor cells significantly decreased after vaccination. Maintenance of WT1 expression, which is the target molecule of immunotherapy, in tumor cells during the vaccination period was significantly associated with a longer progression-free and overall survival. A high expression of HLA class I antigens and low CD4+/CD8+tumor-infiltrating lymphocytes (TIL) ratio in pre-vaccination specimens, were also associated with a good prognosis. No statistically significant difference existed in the number of infiltrating CD3+or CD8+T cells between the pre- and post-vaccination specimens, whereas the number of infiltrating CD4+T cells significantly decreased in the post-vaccination specimens. This study provides insight into the mechanisms of intra-tumoral immune reaction/escape during WT1 peptide vaccine treatment and suggests potential clinical strategies for cancer immunotherapy.