Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes.

By K. Movahedi, Damya Laoui, C. Gysemans, M. Baeten, G. Stangé, J. van den Bossche, M. Mack, D. Pipeleers, P. in’t Veld, P. De Baetselier and 1 more. Cancer Research, 2010

1,167 citations recorded by the source corpus.

Tumor-associated macrophages (TAM) form a major component of the tumor stroma. However, important concepts such as TAM heterogeneity and the nature of the monocytic TAM precursors remain speculative. Here, we show for the first time that mouse mammary tumors contained functionally distinct subsets of TAMs and provide markers for their identification. Furthermore, in search of the TAM progenitors, we show that the tumor-monocyte pool almost exclusively consisted of Ly6C(hi)CX(3)CR1(low) monocytes, which continuously seeded tumors and renewed all nonproliferating TAM subsets. Interestingly, gene and protein profiling indicated that distinct TAM populations differed at the molecular level and could be classified based on the classic (M1) versus alternative (M2) macrophage activation paradigm. Importantly, the more M2-like TAMs were enriched in hypoxic tumor areas, had a superior proangiogenic activity in vivo, and increased in numbers as tumors progressed. Finally, it was shown that the TAM subsets were poor antigen presenters, but could suppress T-cell activation, albeit by using different suppressive mechanisms. Together, our data help to unravel the complexities of the tumor-infiltrating myeloid cell compartment and provide a rationale for targeting specialized TAM subsets, thereby optimally "re-educating" the TAM compartment.

Subfields: Immunology, Oncology

View Paper: https://www.semanticscholar.org/paper/63b6845f0ecc70449e9dbe6ec61e1c1db634d2ca

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

1. A. Mantovani
2. Lisa M. Coussens
3. A. Sica
4. P. Allavena
5. D. Hanahan
6. J. Pollard
7. J. Joyce
8. F. Balkwill

In Oncology

1. A. Mantovani
2. Lisa M. Coussens
3. J. Joyce
4. D. Hanahan
5. P. Allavena
6. J. Pollard
7. A. Sica
8. Rakesh K. Jain

Citations in the corpus

• Tumor-associated macrophages in tumor metastasis: biological roles and clinical therapeutic applications (2019, background): “M1 macrophages secrete proinflammatory cytokines such as IL-12, tumor necrosis factor (TNF)-α, CXCL-10, and interferon (IFN)-γ and produce high levels of nitric oxide synthase (NOS, an enzyme metabolizing arginine to the “killer” molecule nitric oxide), while M2 macrophages secrete anti-inflammatory”
• Role of macrophage targeting in the antitumor activity of trabectedin. (2013, background): “The phenotype of TAM comprises mature (F4/80Ly6C) and immature (F4/80 Ly6C) macrophages (Movahedi et al., 2010; Swirski et al., 2007).”
• Cancer-related inflammation: common themes and therapeutic opportunities. (2012, background): “TAM populations in murine tumors can be quite diverse and hypoxia may be one driver of this [9].”
• Tumor-associated macrophages: from mechanisms to therapy (2014, background): “Nevertheless, several recent studies suggest that most TAM subpopulations arise from the Ly6C+ population of circulating mouse monocytes in grafted tumors (Movahedi et al., 2010), primary mouse mammary tumors (Franklin et al., 2014), and in lung metastases (Qian et al., 2011).”
• Accessories to the crime: functions of cells recruited to the tumor microenvironment. (2012, positive): “…by conventional tissue macrophages (Qian and Pollard, 2010), instead manifesting an ability to block CD8 + T cell proliferation or infiltration though release of factors with immunosuppressive potential (Denardo et al., 2011; Doedens et al., 2010; Kryczek et al., 2006; Movahedi et al., 2010).”
• Developmental and Functional Heterogeneity of Monocytes. (2018, background): “In both cases, the number of circulating Ly6CLow monocytes decrease, while Ly6CHi monocyte numbers remain unaffected (Greter et al., 2012; Hoeffel et al., 2015; Hoeffel and Ginhoux, 2018; MacDonald et al., 2010; Mrdjen et al., 2018).”
• Tumor-Associated Macrophages and Neutrophils in Tumor Microenvironment (2016, background): “For example, within cancerous tissue, TAMs can bemicroanatomically diverse, including the accumulation of cells with protumor properties in hypoxic areas [31] and differences in inflammatory components and pathways between tumors originating in distinct anatomical sites [31, 32].”
• HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PlGF. (2011, background): “Protumoral and proangiogenic (i.e., M2-like) TAMs express elevated levels of the mannose receptor-1 (MRC1), argi- nase-1 (Arg1), IL-10 and the chemokines CCL22 and CCL17 (Movahedi et al., 2010; Pucci et al., 2009).”