Macrophages, innate immunity and cancer: balance, tolerance, and diversity

Mantovani, Alberto; Sica, Antonio

doi:10.1016/j.coi.2010.01.009

Cited by 1,303 publications

(1,211 citation statements)

References 72 publications

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“…Circumstantial evidence suggests that the anti-tumor activity of CD40 agonist antibodies is mediated by macrophage activation. These recent [44] and previous [4] results, including data from patients suggest that it is indeed possible to tip the macrophage balance in an antitumor direction. [10].…”

Section: Therapeutic Targetingmentioning

confidence: 54%

“…Macrophages can act as a double-edged sword in cancer [4,11]. It has long been known that appropriately activated mononuclear phagocytes can express anti-tumor activity in vitro and in vivo by direct killing of tumor cells and/or by eliciting vascular damage and tissue destruction; however, in the Darwinian evolution of tumors, TAMs are co-opted as an integral component of the neoplastic microenvironment.…”

Section: Discussionmentioning

confidence: 99%

“…The first, the extrinsic pathway, is driven by exogenous conditions which cause non-resolving smouldering inflammatory responses; the second, the intrinsic pathway, is triggered by mutation of either oncogenes or tumor suppressor genes that activate the expression of inflammation-related programmes [1]. Macrophages are a key component of cancer-related inflammation (CRI) [1][2][3][4]. In many tumors, a correlation between increased numbers and/or density of macrophages and poor prognosis has been observed [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

“…In particular, we will emphasize the open questions and stumbling blocks to diagnostic and therapeutic exploitation building on previous reviews that provide the framework for the present contribution, which by virtue of being a Viewpoint is restricted in length [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

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Cancer‐promoting tumor‐associated macrophages: New vistas and open questions

et al. 2011

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Tumor‐associated macrophages (TAMs) are key components of the tumor macroenvironment. Cancer‐ and host cell‐derived signals generally drive the functions of TAMs towards an M2‐like polarized, tumor‐propelling mode; however, when appropriately re‐educated. TAMs also have the potential to elicit tumor destructive reactions. Here, we discuss recent advances regarding the immunobiology of TAMs and highlight open questions including the mechanisms of their accumulation (recruitment versus proliferation), their diversity and how to best therapeutically target these cells.

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Section: Therapeutic Targetingmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cancer‐promoting tumor‐associated macrophages: New vistas and open questions

et al. 2011

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“…However, these chemokines are usually associated with pro-rather than anti-tumor activities. For example, CCL2 (MCP-1), which is overexpressed in a wide range of cancers [234], is associated with poor prognosis in breast, colorectal, cervical and thyroid cancers [235][236][237][238][239]. Tumor-derived CCL2 plays a pro-tumor role by recruiting inflammatory monocytes to pulmonary metastases [240] and MDSCs to the tumor microenvironment [241], as well as promoting angiogenesis [242], tumor cell proliferation [243] and migration [244].…”

Section: Neutrophil Activation In Cancermentioning

confidence: 99%

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

Sionov

Fridlender

Granot

2014

Cancer Microenvironment

342

261

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Neutrophils are myeloid cells that constitute 50-70 % of all white blood cells in the human circulation. Traditionally, neutrophils are viewed as the first line of defense against infections and as a major component of the inflammatory process. In addition, accumulating evidence suggest that neutrophils may also play a key role in multiple aspects of cancer biology. The possible involvement of neutrophils in cancer prevention and promotion was already suggested more than half a century ago, however, despite being the major component of the immune system, their contribution has often been overshadowed by other immune components such as lymphocytes and macrophages. Neutrophils seem to have conflicting functions in cancer and can be classified into anti-tumor (N1) and pro-tumor (N2) sub-populations. The aim of this review is to discuss the varying nature of neutrophil function in the cancer microenvironment with a specific emphasis on the mechanisms that regulate neutrophil mobilization, recruitment and activation.

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High CD206 levels in Hodgkin lymphoma‐educated macrophages are linked to matrix‐remodeling and lymphoma dissemination

et al. 2020

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Macrophages (Mφ) are abundantly present in the tumor microenvironment and may predict outcome in solid tumors and defined lymphoma subtypes. Mφ heterogeneity, the mechanisms of their recruitment, and their differentiation into lymphoma‐promoting, alternatively activated M2‐like phenotypes are still not fully understood. Therefore, further functional studies are required to understand biological mechanisms associated with human tumor‐associated Mφ (TAM). Here, we show that the global mRNA expression and protein abundance of human Mφ differentiated in Hodgkin lymphoma (HL)‐conditioned medium (CM) differ from those of Mφ educated by conditioned media from diffuse large B‐cell lymphoma (DLBCL) cells or, classically, by macrophage colony‐stimulating factor (M‐CSF). Conditioned media from HL cells support TAM differentiation through upregulation of surface antigens such as CD40, CD163, CD206, and PD‐L1. In particular, RNA and cell surface protein expression of mannose receptor 1 (MRC1)/CD206 significantly exceed the levels induced by classical M‐CSF stimulation in M2‐like Mφ; this is regulated by interleukin 13 to a large extent. Functionally, high CD206 enhances mannose‐dependent endocytosis and uptake of type I collagen. Together with high matrix metalloprotease9 secretion, HL‐TAMs appear to be active modulators of the tumor matrix. Preclinical in ovo models show that co‐cultures of HL cells with monocytes or Mφ support dissemination of lymphoma cells via lymphatic vessels, while tumor size and vessel destruction are decreased in comparison with lymphoma‐only tumors. Immunohistology of human HL tissues reveals a fraction of cases feature large numbers of CD206‐positive cells, with high MRC1 expression being characteristic of HL‐stage IV. In summary, the lymphoma‐TAM interaction contributes to matrix‐remodeling and lymphoma cell dissemination.

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Macrophages, innate immunity and cancer: balance, tolerance, and diversity

Cited by 1,303 publications

References 72 publications

Cancer‐promoting tumor‐associated macrophages: New vistas and open questions

Cancer‐promoting tumor‐associated macrophages: New vistas and open questions

The Multifaceted Roles Neutrophils Play in the Tumor Microenvironment

High CD206 levels in Hodgkin lymphoma‐educated macrophages are linked to matrix‐remodeling and lymphoma dissemination

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