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

Jing Wang,Bo Guo,Danyang Li,Huaixing Cang

doi:10.1002/cam4.2327

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.

Highlights

The immune‐associated cells in tumor microenvironment are multitudinous, mainly including macrophages, dendritic cells (DCs), myeloid‐derived suppressor cells (MDSCs), T cells, mast cells, and natural killer (NK) cells
Siglec‐15 which was found to be abundant in macrophages but lack in other immune cells or normal human tissues, was suggested to be a macrophage‐associated suppressive molecules to T cells. It was proposed by the in vivo experiment that the siglec‐15 deficient mice was resistive to tumor growth by promoting the responses of T cells,[82] and siglec‐15 is recommended to be a promising target for normalized cancer immunotherapy.[83] programmed cell death ligand 1 (PD‐L1), a ligand for T‐cell inhibitory receptor PD‐1, was suggested to be an active agent in the immune suppression
Growth factors including vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), epidermal growth factor (EGF), TGF‐β, and fibroblast growth factor (FGF) from tumor‐associated macrophage (TAM) are widely regarded as a potential mediator to promote the survival and proliferation of cancer cells,[100] which can be secreted by fibroblasts

Summary

| INTRODUCTION

The immune‐associated cells in tumor microenvironment are multitudinous, mainly including macrophages, dendritic cells (DCs), myeloid‐derived suppressor cells (MDSCs), T cells, mast cells, and natural killer (NK) cells. Immune cells in tumor microenvironment mainly include TAMs, DCs, T cells, NK cells, MDSCs and mast cells, which play diverse roles in tumor procession stages.[1]. The primary TAMs can recruit monocytes to tumor site by secreting chemotactic factors of CCL2, CCL5, CCL7, CXCL8 and CXCL12 which can be polarized to M2‐like phenotype with the stimulation of IL‐4, IL‐6, IL‐10, IL‐13 and transforming growth factor‐beta (TGF‐β).[8,9] Besides, products of tumor‐promoting growth factors from TAMs, such as epidermal growth factor (EGF), make efforts to neovascularization and modulating immune response In this process, the matrix metalloproteinase (MMPs) synthesis which have a significant impact on angiogenesis is regulated by vascular endothelial growth factor (VEGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), and TGF‐β.10-12.

Recognized markers

Angiogenesis in tumor

TAMs in angiogenesis

Growth factors in tumor niche

Other special conditions in tumor niche

| CONCLUSION