Macrophages: A rising star in immunotherapy for chronic pancreatitis
Macrophages: A rising star in immunotherapy for chronic pancreatitis
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DOI：
10.1016/j.phrs.2022.106508
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发表时间：
2022-10-21
影响因子：
9.3
通讯作者：
Dong，Deshi
中科院分区：
文献类型：
--
作者：
Xiang，Hong;Yu，Hao;Dong，Deshi
慢性胰腺炎（CP）是一种慢性消耗性疾病，发病率逐年上升.巨噬细胞作为CP发病机制中的一个重要因素，在CP的早期至晚期的最典型的病理因子中发挥相当大的作用。巨噬细胞相关细胞因子是一种生物标志物，为CP的早期诊断和与胰腺癌及胰腺疾病的鉴别诊断带来了新的可能性。此外，在已建立的CP中，巨噬细胞与T淋巴细胞的相互作用导致免疫失调，并且巨噬细胞分泌促炎细胞因子被认为是腺泡-导管化生（ADM）的有力驱动因素。在晚期CP中，巨噬细胞以自分泌或旁分泌方式与胰腺星状细胞（PSC）和胰岛细胞相互作用，以促进胰腺纤维化和胰岛功能障碍的发展。在这里，我们回顾了巨噬细胞与胰腺腺泡细胞，PSC，其他免疫细胞和胰岛细胞在CP进展的不同阶段的串扰，以及目前针对巨噬细胞的CP免疫治疗，这将有助于解释巨噬细胞在CP中的决定性作用及其作为CP免疫治疗靶点的潜力。此外，巨噬细胞靶向免疫疗法不仅可以在生理学和病理学方面，而且还可以在剂量、形式和递送的进一步优化方面得到改进。这些努力有利于增强巨噬细胞在CP治疗中的靶向性。
Chronic pancreatitis (CP) is a chronic wasting disease with an increasing incidence. As an important factor in the pathogenesis of CP, macrophages play a considerable role in the most typical pathological agents throughout the early to late stages of CP. Macrophage-associated cytokines are biomarkers that bring new possibilities for the early diagnosis of CP and differential diagnosis with pancreatic cancer and pancreatic diseases. In addition, in established CP, macrophage interactions with T lymphocytes leads to immune dysregulation, and macrophage secretion of proinflammatory cytokines is considered a potent driver of acinar-to-ductal metaplasia (ADM). In advanced CP, macrophages interact with pancreatic stellate cells (PSCs) and islet cells in an autocrine or paracrine manner to promote the development of pancreatic fibrosis and islet dysfunction. Here, we review the crosstalk of macrophages with pancreatic acinar cells, PSCs, other immune cells and islet cells at different stages of CP progression, as well as current CP immunotherapies targeting macrophages, which will help explain the decisive role of macrophages in CP and their potential as targets of CP immunotherapy. Furthermore, macrophage-targeted immunotherapy can be advanced, not only in terms of physiology and pathology but also in terms of further optimization of dose, forms and delivery. All these efforts are beneficial to enhancing the targeting of macrophages in the treatment of CP.