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Tumor-Associated Macrophages Case Study

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Introduction
Tumor-associated macrophages (TAMs) are a major cellular component of both mouse and human tumors (Pollard, 2004;
Lewis and Pollard, 2006). High numbers of TAMs in human tumors usually correlate with reduced patient survival (Bingle et al., 2002; Zhang et al., 2012), and studies in mice have shown that TAMs promote important steps in tumor progression including tumor angiogenesis, cancer cell invasion, metastasis, and the suppression of adaptive anti-tumor immunity (Noy and
Pollard, 2014). TAMs also mediate or limit the efficacy of various forms of anti-cancer therapies (De Palma and Lewis, 2013).
Recent fate-mapping experiments have shown that macrophages in steady-state tissues can originate from at least three
different …show more content…

Moreover, TAM distribution can vary between different types of tumor, and between primary or metastatic tumors (Lewis and Pollard, 2006). Importantly, across several types of human tumor, the abundance of a distinct subset of PV macrophages has been shown to correlate with increased tumor angiogenesis, distant metastasis, poor prognosis, and/or the recurrence of tumors after chemotherapy in various forms of cancer (Kurahara et al., 2012; Matsubara et al., 2013; Robinson et al., 2009).
As discussed in later sections, the markers expressed by PV macrophages vary between primary and metastatic tumors.
However, a unifying feature is their proximity to blood vessels
(sometimes making direct contact with endothelial cells or pericytes), or their preference for highly vascularized tumor areas.
This contrasts with the majority of TAMs found elsewhere in tumors
(Lewis and Pollard, 2006). This review discusses recent studies demonstrating an array of tumor-promoting functions for PV macrophages in both primary and secondary tumors
(summarized in Figure 1).
Tumor Angiogenesis
A distinct subset of PV TAMs has been shown to regulate angiogenesis in various mouse primary tumor models and to correlate with microvessel density in human tumors. BM transplant experiments conducted by De Palma et al. (2003, 2005) identified a subset of BM-derived TAMs that cluster around tumor blood vessels and express higher levels of the angiopoietin receptor,
TIE2, and the mannose receptor,

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