Department of Gastroenterology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui Province, People's Republic of China.
Department of Neurosurgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui Province, People's Republic of China.
Cancer Immunol Immunother. 2024 Mar 2;73(4):64. doi: 10.1007/s00262-024-03632-6.
Pancreatic cancer remains a challenging disease with limited treatment options, resulting in high mortality rates. The predominant approach to managing pancreatic cancer patients continues to be systemic cytotoxic chemotherapy. Despite substantial advancements in immunotherapy strategies for various cancers, their clinical utility in pancreatic cancer has proven less effective and durable. Whether administered as monotherapy, employing immune checkpoint inhibitors, tumor vaccines, chimeric antigen receptors T cells, or in combination with conventional chemoradiotherapy, the clinical outcomes remain underwhelming. Extensive preclinical experiments and clinical trials in the realm of pancreatic cancer have provided valuable insights into the complexities of immunotherapy. Chief among the hurdles are the immunosuppressive tumor microenvironment, limited immunogenicity, and the inherent heterogeneity of pancreatic cancer. In this comprehensive review, we provide an overview and critical analysis of current clinical immunotherapy strategies for pancreatic cancer, emphasizing their endeavors to overcome immunotherapy resistance. Particular focus is placed on strategies aimed at reshaping the immunosuppressive microenvironment and enhancing T cell-mediated tumor cell killing. Ultimately, through deeper elucidation of the underlying pathogenic mechanisms of pancreatic cancer and the refinement of therapeutic approaches, we anticipate breakthroughs that will pave the way for more effective treatments in this challenging disease.
胰腺癌仍然是一种具有挑战性的疾病，治疗选择有限，导致死亡率居高不下。管理胰腺癌患者的主要方法仍然是全身性细胞毒性化疗。尽管免疫疗法在各种癌症中的策略取得了实质性进展，但在胰腺癌中的临床效果证明效果较差且持续时间较短。无论是作为单一疗法、使用免疫检查点抑制剂、肿瘤疫苗、嵌合抗原受体 T 细胞，还是与常规化疗放疗联合使用，临床结果都不尽如人意。在胰腺癌领域的广泛临床前实验和临床试验为免疫疗法的复杂性提供了宝贵的见解。其中最大的障碍是免疫抑制性肿瘤微环境、有限的免疫原性和胰腺癌固有的异质性。在这篇全面的综述中，我们概述并批判性地分析了当前用于胰腺癌的临床免疫疗法策略，强调了它们克服免疫疗法耐药性的努力。特别关注旨在重塑免疫抑制性微环境和增强 T 细胞介导的肿瘤细胞杀伤的策略。最终，通过更深入地阐明胰腺癌的潜在发病机制和改进治疗方法，我们预计将在这一具有挑战性的疾病中取得突破，为更有效的治疗方法铺平道路。
