Identification of a Subpopulation of Macrophages in Mammary Tumor–Bearing Mice That Are Neither M1 nor M2 and Are Less Differentiated

Torroella-Kouri, Marta; Silvera, Risset; Rodríguez, Dayron; Caso, Raul; Shatry, Alwi M.; Opiela, Shannon J.; Ilkovitch, Dan; Schwendener, Reto A.; Iragavarapu-Charyulu, Vijaya; Cardentey, Yoslayma; Štrbo, Nataša; López, Diana M.

doi:10.1158/0008-5472.can-08-3427

Cited by 110 publications

(91 citation statements)

References 42 publications

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“…In most established malignant tumors TAMs express an M2-like phenotype, although there are variations and exceptions to this common theme [40]. The TAM phenotype is reversible and these cells can be re-educated to exert antitumor activity [41][42][43].…”

Section: Therapeutic Targetingmentioning

confidence: 99%

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: 99%

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

et al. 2011

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“…They accumulate in the invasive tumor edge, cancer cell/stromal border, central tumor mass, hypoxic/necrotic regions and perivascular areas (16). TAMs have features of a trophic macrophage phenotype (M2), which means that they may remodel the extracellular matrix and suppress the immune system (8,14,17). TAMs produce other mediators and enzymes.…”

Section: Macrophages-general Function In Carcinogenesismentioning

confidence: 99%

“…TAMs modulate the immune reaction by enhancing the synthesis of TGF-β and prostaglandin E2 (PGE2), in addition to reducing the synthesis of Il-12, Il-18 and the TLR signaling pathway, which results in the reduced activation of other cells of immune response (17). They markedly influence the cytotoxic lymphocytes T on which they exert a direct effect (by stimulating the synthesis of arginase and nitrogen oxide that inhibit the effect of cytotoxic T lymphocytes) and an indirect effect (through IL-10 they stimulate monocytes to express the costimulatory molecule PD-L1 which suppresses these lymphocytes, and through the CCL22 chemokine which affects the regulatory T lymphocytes that additionally inhibit them) (9,18).…”

Section: Macrophages-general Function In Carcinogenesismentioning

confidence: 99%

Macrophages in skin melanoma-the key element in melanomagenesis (Review)

Pieniążek¹,

Matkowski

Donizy

2018

Oncol Lett

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Abstract. Cutaneous melanoma is an aggressive cancer and its onset and growth are associated, through direct and indirect interactions, with the cancer microenvironment. The microenvironment comprises a dynamic complex of numerous types of cells (due to histogenesis) that constantly interact with each other through multiple cytokines and signaling proteins. Macrophages are one of the most thoroughly studied pleiotropic cells of the immune system. One of their major cytophysiological functions is their involvement in phagocytosis. Previous studies examining the microenvironment of melanomas and tumor-associated macrophages have revealed that they are involved in all stages of melanomagenesis. In the case of cancer initiation, they form an inflammatory microenvironment and then suppress the anticancer activity of the immune system, stimulate angiogenesis, enhance migration and invasion of the cancer cells, and ultimately contribute to the metastatic process. The present review provides a detailed overview on the function of macrophages in the melanoma microenvironment. IntroductionMelanomas are a rare but aggressive cutaneous type of cancer in humans (1). At the dissemination stage in a majority of cases, the disease is resistant to treatment with cytostatics and radiotherapy (1). Therefore, the identification of novel molecular mechanisms involved in the melanomagenesis process and tumor progression have enabled the production of targeted therapies that yield notable effects (1). The basis for melanomagenesis is the accumulation of genetic disorders in the melanocyte (the most frequent ones include the following mutations: B-Raf proto-oncogene, serine/threonine kinase, N-Ras proto-oncogene, GTPase and phosphatase and tensin homolog) (1). However, only the interaction between microenvironment elements and genetic changes in the melanocyte result in the ultimate transformation of a dysplastic melanocyte into a melanoma cell, and at further stages result in the local invasion and dissemination of the primary lesion (1). It is the microenvironment that is one of the key elements of cancer formation and is being studied at present.A melanoma microenvironment is a markedly heterogenic population of cells that involves fibroblasts, macrophages, lymphocytes, other immune system cells, adipocytes and cells that form the structural elements of cutaneous blood vessels sunk in the extracellular matrix (2). The aforementioned complex network of cellular associations are constantly interacting through direct contact and active protein substances including secretory proteins (e.g., metalloproteinases or

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“…Not only the intratumoral macrophages, but also spleen and peritoneal macrophages of tumor-bearing individuals share these similar immunosuppressive properties and play an important role in tumorigenesis [199,200]. TAMs were also shown to attract CD4 + CD25 + FOXP3 + regulatory T cells [112] that are known to suppress the antitumor function of cytotoxic T cells.…”

Section: Macrophagesmentioning

confidence: 99%

A New Approach to Cancer Therapy: The Tumor Microenvironment as Target

Schwendener¹,

Mete²

2013

Frontiers in Clinical Drug Research - Anti-Cancer Agents

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Solid tumors grow within a complex microenvironment composed of diverse cell types such as fibroblasts, endothelial cells, mast cells, macrophages and immune cells that are attracted by tumor cell derived factors and embedded in an extracellular matrix. Molecular and cellular interactions between epithelial cells and cells surrounding the tumor stroma promote growth, invasion and spread of tumors. To delay or impede tumor growth, the tumor microenvironment (TME) is increasingly being explored as a potential therapeutic target for which novel strategies are developed. lt;/pgt;lt;pgt; This article reviews how key interactions between tumor cells and surrounding mesenchymal and immune cells in the TME can promote tumor progression and it highlights cellular and molecular elements that might represent novel therapeutic targets. Special emphasis is given on therapies targeted towards tumor-associated macrophages. As main class of drugs the bisphosphonates are covered with their properties to repolarize a pro-tumorigenic, immunosuppressive environment to a tumor growth inhibiting and immunocompetent microenvironment. Properties and advantages of liposome-encapsulated bisphosphonates as macrophage depleting or modulating agents as well as the latest developments towards clinical applications of compounds targeting cellular and molecular components of the TME are described and reviewed. This article reviews how key interactions between tumor cells and surrounding mesenchymal and immune cells in the TME can promote tumor progression and it highlights cellular and molecular elements that might represent novel therapeutic targets. Special emphasis is given on therapies targeted towards tumor-associated macrophages. As main class of drugs the bisphosphonates are covered with their properties to repolarize a pro-tumorigenic, immunosuppressive environment to a tumor growth inhibiting and immunocompetent microenvironment. Properties and advantages of liposome-encapsulated bisphosphonates as macrophage depleting or modulating agents as well as the latest developments towards clinical applications of compounds targeting cellular and molecular components of the TME are described and reviewed.

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Identification of a Subpopulation of Macrophages in Mammary Tumor–Bearing Mice That Are Neither M1 nor M2 and Are Less Differentiated

Cited by 110 publications

References 42 publications

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

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

Macrophages in skin melanoma-the key element in melanomagenesis (Review)

A New Approach to Cancer Therapy: The Tumor Microenvironment as Target

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