Macrophages: A rising star in immunotherapy for chronic pancreatitis.

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.