Clinical significance of macrophage heterogeneity in human malignant tumors.
Bottom Line: The fact that various immune cells, including macrophages, can be found in tumor tissue has long been known.With the recent introduction of the novel concept of macrophage differentiation into a classically activated phenotype (M1) and an alternatively activated phenotype (M2), the role of tumor-associated macrophages (TAMs) is gradually beginning to be elucidated.Specifically, in human malignant tumors, TAMs that have differentiated into M2 macrophages act as "protumoral macrophages" and contribute to the progression of disease.
Affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.Show MeSH
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Mentions: It has long been known that many leukocytes including macrophages are present in tumor tissues and that these cells, together with fibroblasts and vascular endothelial cells, form the tumor microenvironment (Fig.1).1–4 Previously, activated macrophages were believed to exhibit antitumor activity by directly attacking tumor cells in the tumor microenvironment.5 However, many recent studies have indicated the protumoral functions of tumor-associated macrophages (TAMs), and thus, TAMs are believed to directly or indirectly promote tumor progression.6–8 Great advances have been made in TAM research over the past dozen years or so, with one of the most significant breakthroughs being the development of immunohistochemical methods for identifying TAMs in tumor tissue. Numerous studies using human samples have been carried out using CD68 as a macrophage marker, whereas CD163 and CD204 have been used as markers of M2 macrophages in recent studies.9,10 Although variability is observed according to tumor tissue type and location, over 80% of immunohistochemical studies using various human tumor tissues have shown that higher numbers of TAMs are associated with worse clinical prognosis.9 Supporting these clinical observations, in vitro experiments using human tumor cells and experiments using animal models indicate that TAMs promote tumor cell growth by suppressing antitumor immunity and inducing angiogenesis.11,12
Affiliation: Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan.