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Review
. 2020 Jul 17;12(7):1946.
doi: 10.3390/cancers12071946.

Pancreatic Macrophages: Critical Players in Obesity-Promoted Pancreatic Cancer

Yaroslav Teper  1 , Guido Eibl  1
Affiliations
Review

Pancreatic Macrophages: Critical Players in Obesity-Promoted Pancreatic Cancer

Yaroslav Teper et al. Cancers (Basel). .

Abstract

Obesity is a known risk factor for the development of pancreatic cancer, one of the deadliest types of malignancies. In recent years it has become clear that the pancreatic microenvironment is critically involved and a contributing factor in accelerating pancreatic neoplasia. In this context obesity-associated chronic inflammation plays an important role. Among several immune cells, macrophages have been shown to contribute to obesity-induced tissue inflammation. This review article summarizes the current knowledge about the role of pancreatic macrophages in early pancreatic cancer development. It describes the heterogenous origin and mixture of pancreatic macrophages, their role in pancreatic endocrine and exocrine pathology, and the impact of obesity on islet and stromal macrophages. A model is postulated, by which during obesity monocytes are recruited into the pancreas, where they are polarized into pro-inflammatory macrophages that drive early pancreatic neoplasia. This occurs in the presence of local inflammatory, metabolic, and endocrine signals. A stronger appreciation and more detailed knowledge about the role of macrophages in early pancreatic cancer development will lead to innovative preventive or interceptive strategies.

Keywords: acinar-to-ductal metaplasia; inflammation; macrophages; obesity; pancreatic cancer.

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Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Role of pancreatic macrophages in obesity-accelerated early pancreatic neoplasia. During obesity, circulating monocytes are recruited into the pancreas where they differentiate into inflammatory macrophages driving acinar-to-ductal metaplasia. Several factors that recruit monocytes into the pancreas (e.g., MCP-1, ICAM-1) and polarize monocytes into inflammatory macrophages (e.g., LPS, leptin) are depicted here but others do exist. A communication between the endocrine and exocrine compartment in the pancreas driving this process is illustrated here as well. MCP-1: monocyte chemoattractant protein-1; ICAM-1: intercellular adhesion molecule 1; LPS: lipopolysaccharide; RANTES: regulated upon activation, normal T cell expressed and presumably secreted; TGF-α: transforming growth factor-alpha; IL-6: interleukin-6; CCK: cholecystokinin.
Figure 2
Figure 2
Intrapancreatic fat. H.E. (hematoxylin and eosin) image of the pancreas of a KC mouse with DIO (diet-induced obesity). The presence of adipocytes within the pancreatic parenchyma can be seen.
See this image and copyright information in PMC

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