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胰腺癌手术治疗后新抗原肽脉冲树突状细胞疫苗治疗:一项回顾性研究

Neoantigen peptide-pulsed dendritic cell vaccine therapy after surgical treatment of pancreatic cancer: a retrospective study.

作者信息

Oyama Koki, Nakata Kohei, Abe Toshiya, Hirotaka Kento, Fujimori Nao, Kiyotani Kazuma, Iwamoto Chika, Ikenaga Naoki, Morisaki Shinji, Umebayashi Masayo, Tanaka Hiroto, Koya Norihiro, Nakagawa Shinichiro, Tsujimura Kenta, Yoshimura Sachiko, Onishi Hideya, Nakamura Yusuke, Nakamura Masafumi, Morisaki Takashi

机构信息

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

出版信息

Front Immunol. 2025 Apr 3;16:1571182. doi: 10.3389/fimmu.2025.1571182. eCollection 2025.

Abstract

INTRODUCTION

Pancreatic cancer shows very poor prognosis and high resistance to conventional standard chemotherapy and immunotherapy; therefore, the development of new breakthrough therapies is highly desirable.

METHOD

We retrospectively evaluated the safety and efficacy of neoantigen peptide-pulsed dendritic cell (Neo-P DC) vaccine therapy after surgical treatment of pancreatic cancer.

RESULT

The result showed induction of neoantigen-specific T cells in 13 (81.3%) of the 16 patients who received Neo-P DC vaccines. In survival analysis of the nine patients who received Neo-P DC vaccines after recurrence, longer overall survival was observed in patients with neoantigen-specific T cell induction than those without T cell induction. Notably, only one of the seven patients who received Neo-P DC vaccines as adjuvant setting developed recurrence, and no patient died during median follow-up 61 months after surgery (range, 25-70 months). Furthermore, TCR repertoire analyses were performed in a case treated with Neo-P DC vaccine combined with long and short peptides, and one significantly dominant clone induced by the long peptide was detected among CD4 T cell populations.

DISCUSSION

The present study suggests the feasibility and efficacy of Neo-P DC vaccine therapy after surgical treatment of pancreatic cancer in both postoperative recurrence cases and adjuvant setting. A case analysis suggests the importance of combination with long peptides targeting CD4 T cell.

摘要

引言

胰腺癌的预后很差,对传统标准化疗和免疫疗法具有高度抗性;因此,非常需要开发新的突破性疗法。

方法

我们回顾性评估了胰腺癌手术治疗后新抗原肽脉冲树突状细胞(Neo-P DC)疫苗治疗的安全性和有效性。

结果

结果显示,在接受Neo-P DC疫苗的16例患者中,有13例(81.3%)诱导出了新抗原特异性T细胞。在对9例复发后接受Neo-P DC疫苗的患者进行的生存分析中,诱导出新抗原特异性T细胞的患者的总生存期长于未诱导出T细胞的患者。值得注意的是,在作为辅助治疗接受Neo-P DC疫苗的7例患者中,只有1例出现复发,在术后中位随访61个月(范围25 - 70个月)期间无患者死亡。此外,对1例接受Neo-P DC疫苗联合长短肽治疗的病例进行了TCR库分析,在CD4 T细胞群体中检测到1个由长肽诱导的显著优势克隆。

讨论

本研究表明,Neo-P DC疫苗治疗在胰腺癌手术治疗后的术后复发病例和辅助治疗中均具有可行性和有效性。病例分析表明了与靶向CD4 T细胞的长肽联合使用的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da2/12004129/4ce69c4aa9df/fimmu-16-1571182-g001.jpg

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