Tumour-associated macrophages and cancer

Cook, Jenny Anne; Hagemann, Thorsten

doi:10.1016/j.coph.2013.05.017

Cited by 149 publications

(145 citation statements)

References 70 publications

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“…In the sporadic intestinal carcinogenesis model, we noted decreased macrophages in both the adenomas and uninvolved intestine associated with CCR6 deficiency. 4 As a tumor-promoting effect of macrophages is supported by several lines of evidence, [12][13][14] we suspected that CCR6 may mediate enhanced adenoma growth through recruitment of macrophages. Thus, we investigated whether CCR6 deficiency decreases infiltrating macrophages in the transplanted tumor, Figure 1.…”

Section: Deficiency Of Host Ccr6 Decreases Infiltration Of Macrophagementioning

confidence: 77%

“…Other molecules such as colony-stimulating factor 2 (CSF-2, also known as granulocyte-macrophage colony-stimulating factor (GM-CSF)), vascular endothelial growth factor (VEGF), Transforming growth factor b (TGF-b), and CXCL12 (also known as stromal cell-derived factor 1 (SDF-1)) have also been shown to be involved in the recruitment of tumor macrophages. [12][13][14] The role of CCL20-CCR6 interactions in monocyte/macrophage recruitment is not well established. In a model of breast cancer development related to expression of a polyoma virus gene, tumor macrophages were found to be decreased in tumors that developed in CCR6-deficient mice.…”

Section: Discussionmentioning

confidence: 99%

“…[12][13][14] Some studies relying on immunohistochemical staining of human colorectal cancers, in fact, indicate that macrophages along the tumor margin [31][32][33] and macrophages expressing VEGF 34 are associated with a good prognosis. Others have suggested that macrophages in colorectal cancer may have co-stimulatory functions in antitumor immunity 35 or may be able to induce tumor cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

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Stromal CCR6 drives tumor growth in a murine transplantable colon cancer through recruitment of tumor-promoting macrophages

et al. 2016

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Interactions between the inflammatory chemokine CCL20 and its receptor CCR6 have been implicated in promoting colon cancer; however, the mechanisms behind this effect are poorly understood. We have previously demonstrated that deficiency of CCR6 is associated with decreased tumor macrophage accumulation in a model of sporadic intestinal tumorigenesis. In this study, we aimed to determine the role of stromal CCR6 expression in a murine syngeneic transplantable colon cancer model. We show that deficiency of host CCR6 is associated with decreased growth of syngeneic CCR6-expressing colon cancers. Colon cancers adoptively transplanted into CCR6-deficient mice have decreased tumor-associated macrophages without alterations in the number of monocytes in blood or bone marrow. CCL20, the unique ligand for CCR6, promotes migration of monocytes in vitro and promotes accumulation of macrophages in vivo. Depletion of tumor-associated macrophages decreases the growth of tumors in the transplantable tumor model. Macrophages infiltrating the colon cancers in this model secrete the inflammatory mediators CCL2, IL-1a, IL-6 and TNFa. Ccl2, Il1a and Il6 are consequently downregulated in tumors from CCR6-deficient mice. CCL2, IL-1a and IL-6 also promote proliferation of colon cancer cells, linking the decreased macrophage migration into tumors mediated by CCL20-CCR6 interactions to the delay in tumor growth in CCR6-deficient hosts. The relevance of these findings in human colon cancer is demonstrated through correlation of CCR6 expression with that of the macrophage marker CD163 as well as that of CCL2, IL1a and TNFa. Our findings support the exploration of targeting the CCL20-CCR6 pathway for the treatment of colon cancer.

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Section: Deficiency Of Host Ccr6 Decreases Infiltration Of Macrophagementioning

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Stromal CCR6 drives tumor growth in a murine transplantable colon cancer through recruitment of tumor-promoting macrophages

et al. 2016

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“…3 While inflammation is increasingly recognized as a factor in determining the predisposition to cancer, 4 the role of p53 in inflammation is not clear. Macrophages from p53 − / − mice produce increased quantities of proinflammatory cytokines in response to LPS, 5 while peritoneal macrophage count and susceptibility to lethal septic shock are increased in p53 − / − mice administered LPS.…”

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confidence: 99%

A unique role for p53 in the regulation of M2 macrophage polarization

Li¹,

et al. 2014

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P53 is critically important in preventing oncogenesis but its role in inflammation in general and in the function of inflammatory macrophages in particular is not clear. Here, we show that bone marrow-derived macrophages exhibit endogenous p53 activity, which is increased when macrophages are polarized to the M2 (alternatively activated macrophage) subtype. This leads to reduced expression of M2 genes. Nutlin-3a, which destabilizes the p53/MDM2 (mouse double minute 2 homolog) complex, promotes p53 activation and further downregulates M2 gene expression. In contrast, increased expression of M2 genes was apparent in M2-polarized macrophages from p53-deficient and p53 mutant mice. Furthermore, we show, in mice, that p53 also regulates M2 polarization in peritoneal macrophages from interleukin-4-challenged animals and that nutlin-3a retards the development of tolerance to Escherichia coli lipopolysaccharide. P53 acts via transcriptional repression of expression of c-Myc (v-myc avian myelocytomatosis viral oncogene homolog) gene by directly associating with its promoter. These data establish a role for the p53/MDM2/c-MYC axis as a physiological 'brake' to the M2 polarization process. This work reveals a hitherto unknown role for p53 in macrophages, provides further insight into the complexities of macrophage plasticity and raises the possibility that p53-activating drugs, many of which are currently being trialled clinically, may have unforeseen effects on macrophage function. Macrophages have key roles in the response to stress, injury, infection and inflammation. The M1 (classically activated macrophages) are induced by lipopolysaccharide (LPS) and cytokines such as interferon-γ (IFNγ) and characterized by the expression of a wide range of proinflammatory genes. M2 (alternatively activated macrophages) are induced by T helper type 2 (Th2) cytokines such as interleukin-4 (IL4) and IL13 and express high levels of anti-inflammatory and tissue repair marker genes. M2 macrophages perform immunoregulatory functions including defense against infection, promotion of angiogenesis and wound healing. 1 Macrophages exist on a continuum between M1 and M2 subtypes undergoing dynamic changes between these different functional states depending on changes in their microenvironment. This 'plasticity' involves extensive changes in macrophage gene sets and provides the potential to develop drugs to manipulate the macrophage subtype. 2 As such, macrophage polarization, and its molecular basis, has been vigorously researched in recent years.P53 has a crucial role in cancer by controlling the expression of genes involved in apoptosis, cell cycle arrest, metabolism and DNA repair. 3 While inflammation is increasingly recognized as a factor in determining the predisposition to cancer, 4 the role of p53 in inflammation is not clear. Macrophages from p53 − / − mice produce increased quantities of proinflammatory cytokines in response to LPS, 5 while peritoneal macrophage count and susceptibility to lethal septic shock are increased in p53 − ...

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“…In the same manner, Ségaliny et al demonstrated that osteosarcoma cells expressed IL-34, increasing the recruitment of M2-polarised macrophages into the tumour tissue, which correlates with tumour vascularization and the metastatic process [50]. TAMs accumulate in tumour microenvironment and according to their M2 or M1 phenotype contribute to tumour growth, angiogenesis and metastasis [51]. RANK is present at the cell membrane of monocytes/macrophages and RANKL acts as chemoatractant factor for these cells [52].…”

Section: Tumour-associated Macrophages (Tams)mentioning

confidence: 94%

Immune Environment and Osteosarcoma

Heymann¹,

Heymann²

2017

Osteosarcoma - Biology, Behavior and Mechanisms

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Immune niche with its huge cell diversity including more speciically tumour iniltrating lymphocytes (TILs), tumour-associated macrophages (TAMs) regulate osteosarcoma (OS) microenvironment. TAMs exert diferential activities in the tumour development according to their polarisation. Indeed, in oncology, M1-polarised macrophages are considered as anti-tumour efectors, and M2-polarised macrophages are deined as protumour modulators by increasing the neoangiogenic process. TAM density is correlated with tumour cell proliferation, invasion, metastasis and poor prognosis in various epithelial and haematological cancers and in bone metastasis. Similarly, tumour iniltrating lymphocytes play a key role in tumour development by inducing a local tolerant environment favourable for the tumour growth. The present chapter will describe the main roles of the immune system in the pathogenesis of osteosarcoma and the most recent therapeutic development based on its regulation.

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Tumour-associated macrophages and cancer

Cited by 149 publications

References 70 publications

Stromal CCR6 drives tumor growth in a murine transplantable colon cancer through recruitment of tumor-promoting macrophages

Stromal CCR6 drives tumor growth in a murine transplantable colon cancer through recruitment of tumor-promoting macrophages

A unique role for p53 in the regulation of M2 macrophage polarization

Immune Environment and Osteosarcoma

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