Dual Role of Macrophage in Tumor Immunity

Abstract

Macrophages are significant in immune responses, assuming a defensive role. In contrast, macrophages often cause undesirable changes. These reactions are processes by which macrophages express different functional programs in response to microenvironmental signals, defined as M1/M2 polarization. Tumor immunity has been acknowledged for contributing to the elucidation of the mechanism and clinical application in cancer therapy. One of the mechanisms for the refractoriness to cancer immunotherapy is the production of inhibitory cytokines by tumor cells or macrophages. Therefore, therapeutic strategy targeting macrophage or macrophage-derived cytokines may be effective and attractive. This review aims to investigate macrophage-associated pathophysiology and biological behavior in cancers, especially related to microenvironment, such as hypoxia, and current topics regarding some therapies involving macrophages.

M2b macrophage polarization and its roles in diseases

“…Within the tumor, macrophages are a major stromal component, in which they are commonly termed TAM, which exhibit functions similar to M2 macrophages and can be characterized as the M2d subtype . Among tumor‐infiltrating cells in some cancers, macrophages represent the largest population of cells, contributing to at least one‐third of the total tumor mass .…”

“…Among tumor‐infiltrating cells in some cancers, macrophages represent the largest population of cells, contributing to at least one‐third of the total tumor mass . Mounting evidences have shown that M2d macrophages can release some factors that directly stimulate tumor cell survival, proliferation, motility, and angiogenesis, and affect the tumor microenvironment via paracrine cytokines, leading to tumor metastasis and invasion …”

“…Within the tumor, macrophages are a major stromal component, in which they are commonly termed TAM, which exhibit functions similar to M2 macrophages and can be characterized as the M2d subtype. [20][21][22]157 Among tumor-infiltrating cells in some cancers, macrophages represent the largest population of cells, contributing to at least one-third of the total tumor mass. [158][159][160] Mounting evidences have shown that M2d macrophages can release some factors that directly stimulate tumor cell survival, proliferation, motility, and angiogenesis, and affect the tumor microenvironment via paracrine cytokines, leading to tumor metastasis and invasion.…”

“…[158][159][160] Mounting evidences have shown that M2d macrophages can release some factors that directly stimulate tumor cell survival, proliferation, motility, and angiogenesis, and affect the tumor microenvironment via paracrine cytokines, leading to tumor metastasis and invasion. 8,11,12,157,161,162 In addition to M2d, other subtypes of macrophage are present in tumor tissues and play important roles in tumor survival, metas-tasis, and invasion. M1 macrophages are proinflammatory, promote Th1 responses, and display tumoricidal activity by producing large amounts of toxic intermediates (NO and ROS).…”

Macrophage-derived SPARC Attenuates M2-mediated Pro-tumour Phenotypes

“…In contrast, M2 produces various anti-inflammatory factors that not only inhibit the immune system but also promote tumour angiogenesis, proliferation, invasion, metastasis and anti-apoptosis. As the major macrophage subtype in the tumour foci, M2 macrophages are involved in all aspects of tumour development and are also called tumour-associated macrophages (TAMs) [5,10,11].…”