Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related mortality in the United States, with poor overall survival across all stages. Less than 20% of patients are eligible for curative surgical resection at diagnosis, and despite adjuvant chemotherapy, most will experience disease recurrence within two years. The incorporation of immune-based strategies in the adjuvant setting remains an area of intense investigation with unrealized promise. It offers the potential of providing durable disease control for micro-metastatic disease following curative intent surgery and enabling personalized treatments based on mutational neoantigen profiles derived from resected specimens. However, most of these attempts have failed to demonstrate significant clinical success, likely due to the immunosuppressive tumor microenvironment (TME) and individual genetic heterogeneity. Despite these challenges, immune-based strategies, such as therapeutic vaccines targeted towards neoantigens, have demonstrated promise via immune activation and induction of T-cell tumor infiltration. In this review, we will highlight the foundational lessons learned from previous clinical trials of adjuvant immunotherapy, discussing the knowledge gained from analyses of trials with disappointing results. In addition, we will discuss how these data have been incorporated to design new agents and study concepts that are proving to be exciting in more recent trials, such as shared antigen vaccines and combination therapy with immune-checkpoint inhibitors and chemotherapy. This review will evaluate novel approaches in ongoing and future clinical studies and provide insight into how these immune-based strategies might evolve to address the unique challenges for treatment of PDAC in the adjuvant setting.
胰腺导管腺癌（PDAC）是美国癌症相关死亡的第三大原因，各分期总体生存率均较差。诊断时仅有不到20%的患者适合接受根治性手术切除，且尽管进行辅助化疗，大多数患者仍会在两年内出现疾病复发。在辅助治疗中引入免疫策略仍是一个研究热点领域，其潜力尚未完全实现。该策略有望为根治性手术后存在的微转移病灶提供持久的疾病控制，并基于切除标本的突变新抗原谱实现个体化治疗。然而，由于免疫抑制性肿瘤微环境（TME）及个体遗传异质性等因素，多数尝试未能取得显著的临床成功。尽管面临这些挑战，针对新抗原的治疗性疫苗等免疫策略已通过激活免疫反应和诱导T细胞肿瘤浸润展现出潜力。本综述将重点总结既往辅助免疫治疗临床试验的基础经验，探讨从结果不尽人意的试验分析中获得的启示。此外，我们将讨论如何利用这些数据设计新型药物和研究方案——例如共享抗原疫苗、免疫检查点抑制剂联合化疗等策略，这些方案在近期试验中已展现出令人振奋的结果。本文还将评估当前及未来临床研究中的创新方法，并深入探讨这些免疫策略如何发展以应对PDAC辅助治疗中的独特挑战。
Immune-Based Strategies for Pancreatic Cancer in the Adjuvant Setting
肿瘤(癌症)患者之家