Tumor-associated macrophage

Tumor-associated macrophages (TAMs) are the multifarious group of cells that originate mainly from the peritumoral tissue or bone marrow and can be divided into two main types: M1 and M2. Among them are the infiltrating M1 tumor-associated macrophages present in the early stages of tumorigenesis, which can secrete proinflammatory cytokines and in turn inhibit tumor growth. On the contrary, M2 tumor-associated macrophages are predominant in the late stage of tumor formation. Type II cytokines, which are secreted by them, can promote anti-inflammatory reaction and thus promote tumor growth. However, it remains unclear when M1 tumor-associated macrophages are transformed to M2 tumor-associated macrophages, but tumor hypoxia is currently thought to be associated with such a shift. M2 tumor-associated macrophages secrete many proteases such as cathepsin, cytokines, and an epidermal growth factor. The presence of M2 TAMs make the tumor prone to growth and angiogenesis, which in turn damages other tissues. 

Clinically, in 128 patients in the first or second stage of breast cancer it was found that more patients with M2 tumor-associated macrophages had a higher degree of histology, more angiogenesis, and worse overall survival. Patients with more M1 tumor-associated macrophages displayed the opposite effect. .

Macrophages are the most common cells in breast tumors. They have a profound effect on the immune status of tumor tissues. Macrophages act as professional phagocytes in the body, specifically killing and eliminating cells or microbes that are perceived to be a threat. They represent the first line of defence and the bridge of connecting the innate and adaptive arms of the immune system. However, the large number of tumor cells and the derived factors present within the tumour microenvironment (TME) act to attenuate the tumoricidal activity function of macrophages. The TME consists of hypoxic conditions, growth factors and immunosuppressive cytokines that convert trophic macrophages to tumor-associated macrophages (TAM). These features promote tissue growth and repair and are an integral part of development so that macrophages within breast tumors are inadvertently authorized to promote tumor growth and metastasis.

The function of TAMs is controversial as there is growing evidence for their involvement in both pro-tumor (e.g. promotion of growth and metastasis through tumor angiogenesis) as well as anti-tumor (tumoricidal and tumorostatic) processes. TAMs interact with a wide range of growth factors, cytokines and chemokines in the tumor microenvironment which is thought to educate the TAMs and determine their specific phenotype and hence functional role, as the microenvironment varies between different types of tumors. TAMs have therefore been shown to differ in their roles depending on the type of tumor with which they are associated.

Tumor-associated macrophages are mainly of the M2 phenotype, and seem to actively promote tumor growth.

The designation of M1 and M2 polarization states over-simplify macrophage biology, since at least six different TAM subpopulations are known. Therefore, TME TAM phenotype descriptors are likely important.

This page was last edited on 2 March 2018, at 06:37.
Reference: https://en.wikipedia.org/wiki/Tumour-associated_macrophage under CC BY-SA license.

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