Zhao Yutong, Qin Cheng, Lin Chen, Li Zeru, Zhao Bangbo, Li Tianyu, Zhang Xiangyu, Wang Weibin
Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100023, PR China; Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing 100023, PR China; National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Beijing 100023, PR China.
Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100023, PR China; Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing 100023, PR China; National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Beijing 100023, PR China.
Biochim Biophys Acta Rev Cancer. 2024 Nov;1879(6):189183. doi: 10.1016/j.bbcan.2024.189183. Epub 2024 Sep 18.
Pancreatic ductal adenocarcinoma (PDAC) is a digestive system malignancy characterized by challenging early detection, limited treatment alternatives, and generally poor prognosis. Although there have been significant advancements in immunotherapy for hematological malignancies and various solid tumors in recent decades, with impressive outcomes in recent preclinical and clinical trials, the effectiveness of these therapies in treating PDAC continues to be modest. The unique immunological microenvironment of PDAC, especially the abnormal distribution, complex composition, and variable activation states of tumor-infiltrating immune cells, greatly restricts the effectiveness of immunotherapy. Undoubtedly, integrating data from both preclinical models and human studies helps accelerate the identification of reliable molecules and pathways responsive to targeted biological therapies and immunotherapies, thereby continuously optimizing therapeutic combinations. In this review, we delve deeply into how PDAC cells regulate the immune microenvironment through complex signaling networks, affecting the quantity and functional status of immune cells to promote immune escape and tumor progression. Furthermore, we explore the multi-modal immunotherapeutic strategies currently under development, emphasizing the transformation of the immunosuppressive environment into an anti-tumor milieu by targeting specific molecular and cellular pathways, providing insights for the development of novel treatment strategies.
胰腺导管腺癌（PDAC）是一种消化系统恶性肿瘤，其特点是早期检测困难、治疗选择有限且总体预后较差。尽管近几十年来血液系统恶性肿瘤和各种实体瘤的免疫治疗取得了重大进展，在最近的临床前和临床试验中取得了令人瞩目的成果，但这些疗法在治疗PDAC方面的效果仍然一般。PDAC独特的免疫微环境，特别是肿瘤浸润免疫细胞的异常分布、复杂组成和可变激活状态，极大地限制了免疫治疗的效果。毫无疑问，整合临床前模型和人体研究的数据有助于加速识别对靶向生物疗法和免疫疗法有反应的可靠分子和途径，从而不断优化治疗组合。在这篇综述中，我们深入探讨了PDAC细胞如何通过复杂的信号网络调节免疫微环境，影响免疫细胞的数量和功能状态，以促进免疫逃逸和肿瘤进展。此外，我们还探讨了目前正在开发的多模式免疫治疗策略，强调通过靶向特定的分子和细胞途径将免疫抑制环境转化为抗肿瘤环境，为新型治疗策略的开发提供见解。
