Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation

Solinas, Graziella; Germano, Giovanni; Mantovani, Alberto; Allavena, Paola

doi:10.1189/jlb.0609385

Cited by 1,271 publications

(1,148 citation statements)

References 137 publications

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“…Further differentiating in mature tumor-associated macrophages (TAM) in the local microenvironment ( Fig. 1), these cells are key inflammatory components of the cancer stroma, able to affect different aspects of the neoplastic tissue [32,33].…”

Section: Chemokine Regulation Of Leukocyte Attraction Within Tumorsmentioning

confidence: 99%

Chemokines in cancer related inflammation

Allavena

Germano

Marchesi

et al. 2011

Experimental Cell Research

199

140

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Chemokines are key players of the cancer-related inflammation. Chemokine ligands and receptors are downstream of genetic events that cause neoplastic transformation and are abundantly expressed in chronic inflammatory conditions which predispose to cancer. Components of the chemokine system affect multiple pathways of tumor progression including: leukocyte recruitment, neo-angiogenesis, tumor cell proliferation and survival, invasion and metastasis.Evidence in pre-clinical and clinical settings suggests that the chemokine system represents a valuable target for the development of innovative therapeutic strategies

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Section: Chemokine Regulation Of Leukocyte Attraction Within Tumorsmentioning

confidence: 99%

Chemokines in cancer related inflammation

Allavena

Germano

Marchesi

et al. 2011

Experimental Cell Research

199

140

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show abstract

“…42,43 Given that MCP-1 has been implicated as the most important chemokine for macrophage recruitment into the tumor microenvironment, we next examined the effect of MCP-1 deficiency on select macrophage markers in the mammary tissue and tumor microenvironment. In the past several years, considerable progress has been made in distinguishing macrophages from dendritic cells, 2 immune cells of similar origin reflected by overlapping functions and molecular profiles.…”

Section: Discussionmentioning

confidence: 99%

Loss of monocyte chemoattractant protein-1 expression delays mammary tumorigenesis and reduces localized inflammation in the C3(1)/SV40Tag triple negative breast cancer model

Cranford

Velázquez

Enos

et al. 2017

Cancer Biology & Therapy

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Monocyte chemoattractant protein 1 (MCP-1) has been implicated as a major modulator in the progression of mammary tumorigenesis, largely due to its ability to recruit macrophages to the tumor microenvironment. Macrophages are key mediators in the connection between inflammation and cancer progression and have been shown to play an important role in tumorigenesis. Thus, MCP-1 may be a potential therapeutic target in inflammatory and difficult-to-treat cancers such as triple negative breast cancer (TNBC). We examined the effect of MCP-1 depletion on mammary tumorigenesis in a model of TNBC. Tumor measurements were conducted weekly (until 22 weeks of age) and at sacrifice (23 weeks of age) in female C3(1)/SV40Tag and C3(1)/SV40Tag MCP-1 deficient mice to determine tumor numbers and tumorvolumes. Histopathological scoring was performed at 12 weeks of age and 23 weeks of age. Gene expression of macrophage markers and inflammatory mediators were measured in the mammary gland and tumor microenvironment at sacrifice. As expected, MCP-1 depletion resulted in decreased tumorigenesis, indicated by reduced primary tumor volume and multiplicity, and a delay in tumor progression represented by histopathological scoring (12 weeks of age). Deficiency in MCP-1 significantly downregulated expression of macrophage markers in the mammary gland (Mertk and CD64) and the tumor microenvironment (CD64), and also reduced expression of inflammatory cytokines in the mammary gland (TNFa and IL-1b) and the tumor microenvironment (IL-6). These data support the hypothesis that MCP-1 expression contributes to increased tumorigenesis in a model of TNBC via recruitment of macrophages and subsequent increase in inflammatory mediators.

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“…This cellular infiltration includes several immune cells such as lymphoid cells, macrophages, granulocytes, mast cells, dendritic cells, and natural killer cells. Several studies have reported that approximately 50% of the breast tumor mass comprised of macrophages (81)(82)(83). Macrophages have also been implicated in promoting tumor initiation, progression, invasion, and metastases (84,85).…”

Section: Inflammation and Breast Cancermentioning

confidence: 99%

Hormonal regulation of immune modulators in human breast tissue

Morad¹

2015

Linköping University Medical Dissertations

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Breast cancer is the most common form of cancer and the second leading cause of malignancy-associated death in women worldwide. Estrogens are the main sex hormones in women. They are essential for the development and function of normal breast mammary glands; however, prolonged exposure to estrogens increases the risk of breast cancer development and progression. Approximately two-thirds of all breast cancer patients are positive for estrogen receptor (ER), but only 50% of those cases can benefit from antiestrogen therapy. In this thesis we investigated the effects of estrogen, diet modification, and anti-estrogen drugs on several immune modulators in normal human breast tissue. We used the microdialysis technique to sample the immune modulators in situ in normal human breast tissue, in malignant breast tissue, and in tumor tissue from both the immune competent mice with murine breast cancer and immune deficient mice bearing human breast tumors. Furthermore, we also used ex vivo culture of normal breast tissue and in vitro cell culture of breast cancer cell lines. A combined cell culture (co-culture) of breast cancer cell lines, together with the primary mature adipocytes, was also used in this thesis. In Paper I and Paper II, our results suggested that estrogen exerted both proinflammatory and pro-tumorigenic effects in normal human breast tissue. Estradiol increased extracellular interleukin-1β (IL-1β) and leptin levels and decreased IL-1Ra and adiponectin levels in normal human breast tissue. In contrast, tamoxifen decreased IL-1β and leptin levels and increased IL-1Ra and adiponectin levels, shifting the environment towards an antiinflammatory and antitumorigenic state. Diet modification with flaxseed for 30 days also increased IL-1Ra levels, creating an anti-inflammatory environment in normal breast tissue. In the breast cancer tissue, we found that extracellular IL-1β levels and leptin levels were significantly higher, whereas adiponectin levels were significantly lower, compared with normal adjacent breast tissue, which suggested a more proinflammatory state. In the third paper, our in vivo investigation of normal breast tissue revealed significant correlations between vascular endothelial growth factor (VEGF) and leptin, IL-1β and leptin, and between VEGF and IL-1β. No correlations were found in the abdominal subcutaneous (s.c.) fat tissue. Our in vitro inhibition experiments suggested that VEGF was a potent regulator of leptin, but that leptin was not a potent regulator of VEGF. Co-culture per se altered the release of VEGF and leptin and enhanced the effects of estradiol, compared with monocultures of the included cell types. In conclusion, the results presented in this thesis will increase the overall understanding of the role of estrogens in breast cancer, which may be useful in future treatment studies

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Tumor-associated macrophages (TAM) as major players of the cancer-related inflammation

Cited by 1,271 publications

References 137 publications

Chemokines in cancer related inflammation

Chemokines in cancer related inflammation

Loss of monocyte chemoattractant protein-1 expression delays mammary tumorigenesis and reduces localized inflammation in the C3(1)/SV40Tag triple negative breast cancer model

Hormonal regulation of immune modulators in human breast tissue

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