胰腺癌空间构型与新辅助治疗和根治性切除术后疾病复发相关
Spatial Configuration of Pancreatic Cancer Is Associated with Disease Recurrence after Neoadjuvant Therapy and Curative-Intent Resection.
从标准H&E切片量化的残留癌-间质拓扑结构在PDAC新辅助治疗后产生独立预后信号,为空间风险提供细胞免疫相关性依据,并推动前瞻性验证及空间信息指导的辅助治疗策略。
英文原题:Neoantigen peptide-pulsed dendritic cell vaccine therapy after surgical treatment of pancreatic cancer: a retrospective study.
本研究提示,胰腺癌手术治疗后采用Neo-P DC疫苗疗法在术后复发和辅助治疗情境中均具有可行性和疗效。一例病例分析提示,与靶向CD4+ T细胞的长肽联合使用具有重要意义。
胰腺癌预后极差,对常规标准化疗和免疫治疗高度耐药;因此,开发新的突破性疗法极为迫切。
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)疫苗疗法的安全性和有效性。
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,与新抗原特异性 T 细胞未诱导的患者相比,诱导出新抗原特异性 T 细胞的患者观察到更长的总生存期。值得注意的是,在 7 例接受 Neo-P DC 疫苗作为辅助治疗的患者中,仅 1 例出现复发,且在中位随访 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 疫苗联合长肽和短肽治疗的病例进行了 TCR repertoire 分析,在 CD4 + T 细胞群中检测到 1 个由长肽诱导的显著优势克隆。
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.
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