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.