Crosstalk between cancer and immune cells: Role of tumor-associated macrophages in the tumor microenvironment

Abstract

Tumor microenvironment is a complex system that contains multiple cells and cytokines. Among the multiple immune cells, macrophage is particularly abundant and plays an important role throughout the tumor progression process, namely, tumor-associated macrophage (TAM) in this special tumor microenvironment. Many kinds of cytokines from TAMs and other immune cells in tumor niche are involved in the linkage of inflammation, immunity and tumorigenesis. Inflammatory responses induced by TAMs are crucial to tumor development of different stages. This review highlights the critical role of TAMs in the linkage of inflammation, immunity, and cancer. It outlines the molecules of inflammatory cytokines, chemokines, and growth factors mainly from TAMs in tumor microenvironment and their functions in tumor development during the major issues of angiogenesis, chronic inflammation, and immune suppression. Additionally, the signaling pathways involved in tumor progression and the crosstalk between them are also summarized.

Keywords: TAMs; angiogenesis; chronic inflammation; immune suppression; tumor.

Figure 1

The role of TAM in tumor development via the cooperation of angiogenesis, chronic inflammation and immune suppression. Abbreviations: EGF, epidermal growth factor; IL‐10, interleukin‐10; M‐CSF, macrophage colony‐stimulating factor; MMP, matrix metalloproteinase; PGE2, prostaglandin E2; TAM, tumor‐associated macrophage; TGF‐β, transforming growth factor‐beta

Figure 2

The main cytokines and special conditions in tumor microenvironment. Abbreviations: ECM, extracellular matrix; EGF, epidermal growth factor; IL, interleukin; MCP‐1, monocyte chemotactic protein‐1; MDSC, myeloid‐derived suppressor cell; MIP‐1α,β, macrophage inflammatory protein‐1α,β; MMP, matrix metalloproteinase; PDGF, platelet derived growth factor; PGE2, prostaglandin E2; ROS, reactive oxygen species; TGF, transforming growth factor; VEGF, vascular endothelial growth factor

Figure 3

Tumor‐associated signaling pathways and their contributions. Abbreviations: ECM, extracellular matrix; IFN‐γ, interferon‐γ; IL, interleukin; MMP, matrix metalloproteinase; NF‐κB, nuclear factor‐κB; PD‐L1, programmed cell death ligand 1; STAT3, signal transduction and transcription activator 3; TGF‐β, transforming growth factor‐beta; TNF‐α, tumor necrosis factor alpha; VEGF, vascular endothelial growth factor