Macrophages in pancreatic cancer: An immunometabolic perspective

As one of the most fatal gastrointestinal cancers, pancreatic cancer (PC) has a long-term survival rate that has shown limited improvement during recent decades and remains dismal. The poor prognosis is attributed to challenges in early detection, low opportunity for radical resection and resistance to chemotherapy and radiation. Macrophages are one of the most abundant infiltrating immune cells in PC stroma, and they can crosstalk with cancer cells, adipocytes and other stromal cells to modulate metabolism, inflammation and immune status, create an immunosuppressive tumor microenvironment (TME), and ultimately facilitate tumor initiation and progression. In this review, we summarize recent advances in our understanding of macrophage origin, distribution and polarization, as well as provide a thorough review of the role macrophages in PC carcinogenesis and development, as well as the underlying molecular mechanism. Additionally, we investigated macrophage targets in preclinical and clinical trials to evaluate their potential therapeutic value in PC.