胰腺癌(PC)仍然是上消化道癌的主要类型,与发病率升高和存活率低于12%有关。虽然免疫疗法给大多数实体瘤的治疗标准带来了革命性的变化,它在PC中的应用受到寒冷肿瘤微环境的阻碍,以免疫抑制细胞的存在为标志。PC中的适度响应率归因于,部分是阻碍全身免疫疗法的纤维化基质。Further,免疫相关不良事件(iRAE)的发生通常需要使用亚治疗剂量或停止治疗.在追求创新的方法,以提高免疫疗法对PC的有效性,可植入给药装置和支架作为有希望的策略出现.这些技术提供了直接向肿瘤部位持续输送药物的潜力,克服基质障碍,免疫抑制,T细胞排斥,免疫疗法抗性,优化药物剂量,减轻全身毒性。这篇综述提供了胰腺导管腺癌(PDAC)的全面探索,最常见和最激进的PC形式,伴随着对微环境对成功的组合免疫治疗方法的发展提出的挑战的批判性分析。尽管努力,迄今为止,这些方法在提高PDAC治疗结局方面存在不足.审查随后将深入研究完善交付战略的迫切需要,提供了PDAC局部免疫治疗领域过去和正在进行的研究。解决这些问题将为开发有效的新疗法奠定基础,从而增强治疗反应,患者生存,以及诊断为PDAC的个体的总体生活质量。
Pancreatic cancer (PC) remains the predominant type of upper gastrointestinal tract cancer, associated with heightened morbidity and a survival rate below 12%. While immunotherapy has brought about transformative changes in the standards of care for most solid tumors, its application in PC is hindered by the \'\'cold tumor\'\' microenvironment, marked by the presence of immunosuppressive cells. Modest response rates in PC are attributed, in part to, the fibrotic stroma that obstructs the delivery of systemic immunotherapy. Furthermore, the occurrence of immune-related adverse events (iRAEs) often necessitates the use of sub-therapeutic doses or treatment discontinuation. In the pursuit of innovative approaches to enhance the effectiveness of immunotherapy for PC, implantable drug delivery devices and scaffolds emerge as promising strategies. These technologies offer the potential for sustained drug delivery directly to the tumor site, overcoming stromal barriers, immunosuppression, T cell exclusion, immunotherapy resistance, optimizing drug dosage, and mitigating systemic toxicity. This review offers a comprehensive exploration of pancreatic ductal adenocarcinoma (PDAC), the most common and aggressive form of PC, accompanied by a critical analysis of the challenges the microenvironment presents to the development of successful combinational immunotherapy approaches. Despite efforts, these approaches have thus far fallen short in enhancing treatment outcomes for PDAC. The review will subsequently delve into the imperative need for refining delivery strategies, providing an examination of past and ongoing studies in the field of localized immunotherapy for PDAC. Addressing these issues will lay the groundwork for the development of effective new therapies, thereby enhancing treatment response, patient survival, and overall quality of life for individuals diagnosed with PDAC.