Role of tumor-associated macrophages in tumor progression and invasion

Mantovani, Alberto; Schioppa, Tiziana; Porta, Chiara; Allavena, Paola; Sica, Antonio

doi:10.1007/s10555-006-9001-7

Cited by 782 publications

(644 citation statements)

References 76 publications

(103 reference statements)

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“…[29][30][31] TAMs derive from circulating monocytes, which are selectively recruited to the tumor microenvironment by locally produced chemotactic factors. 32,33 metastasis. 5,6,34 Furthermore, TAMs contribute to tumor progression by secretion of factors that enhance neo-angiogenesis.…”

Section: Tumor Immunologymentioning

confidence: 99%

The lymphocyte/monocyte ratio predicts poor clinical outcome and improves the predictive accuracy in patients with soft tissue sarcomas

et al. 2014

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Increasing evidence indicates the involvement of inflammation and coagulation in cancer progression and metastases. Inflammatory biomarkers hold great promise for improving the predictive ability of existing prognostic tools in cancer patients. In the present study, we investigated several inflammatory indices with regard to their prognostic relevance for predicting clinical outcome in soft tissue sarcoma (STS) patients. Three hundred and forty STS patients were divided into a training set (n 5 170) and a validation set (n 5 170). Besides well-established clinico-pathological prognostic factors, we evaluated the prognostic value of the neutrophil/lymphocyte (N/L) ratio, the lymphocyte/monocyte (L/M) ratio and the platelet/lymphocyte (P/L) ratio using Kaplan-Meier curves and univariate as well as multivariate Cox regression models. Additionally, we developed a nomogram by supplementing the L/M ratio to the well-established Kattan nomogram and evaluated the predictive accuracy of this novel nomogram by applying calibration and Harrell's concordance index (c-index). In multivariate analysis, a low L/M ratio was significantly associated with decreased CSS and DFS (HR 5 0.41, 95% CI 5 0.18-0.97, p 5 0.043; HR 5 0.39, 95% CI 5 0.16-0.91, p 5 0.031, respectively) in the training set. Using the validation set for confirmation, we found also in multivariate analysis an independent value for CSS (HR 5 0.33, 95% CI 5 0.12-0.90, p 5 0.03) and for DFS (HR 5 0.36, 95% CI 5 0.16-0.79, p 5 0.01). The estimated c-index was 0.74 using the original Kattan nomogram and 0.78 when the L/M ratio was added. Our study reports for the first time that the pre-operative L/M ratio represents a novel independent prognostic factor for prediction the clinical outcome in STS patients. This easily determinable biomarker might be helpful in improved individual risk assessment.Soft tissue sarcomas (STS) account for nearly 11,280 cases per year and are responsible for about 3,900 deaths in the United States annually, mainly due to local recurrence or metastatic disease. 1 Therefore, it is crucial to understand the biological mechanisms that contribute to tumor progression and to identify novel prognostic markers to generate individualized treatment and follow-up schedules. In a large retrospective study of 2,136 STS patients, Kattan et al. developed a postoperative prognostic model that predicts sarcomaspecific death, based on traditional prognostic factors such as age at diagnosis, tumor size, histologic grade, histologic subtype, tumor depth and site. 2 This nomogram is useful for general risk assessment and has potential value in determining surgical strategy and adjuvant management. Nevertheless, novel prognostic factors might be helpful in improving its predictive ability. Current approaches in cancer research have focused on the characterization of novel biomarkers, which ideally should be easily accessible, highly reproducible, cheap and most importantly, identify patients at high risk for disease-recurrence and death. Increasing evidence su...

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Section: Tumor Immunologymentioning

confidence: 99%

The lymphocyte/monocyte ratio predicts poor clinical outcome and improves the predictive accuracy in patients with soft tissue sarcomas

et al. 2014

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“…Chemokines secreted by senescent stroma such as CXCL1 and IL8 may attract macrophages, and subsequently modulate their function; for example, converting anti-infectious M1 into the pro-carcinogenic M2 phenotype (Mantovani et al, 2004). M2 macrophages have been shown to secrete their own array of signalling molecules, which directly stimulate the epithelium, cause further inflammatory stimulation, and promote angiogenesis (Mantovani et al, 2006). M2 macrophages also have a diminished capacity for antigen presentation, which would promote the survival of neoplastic clones (Mantovani et al, 2004).…”

Section: Mediators Of Epithelial Carcinogenesis In the Aged Or Senescmentioning

confidence: 99%

Profiling influences of senescent and aged fibroblasts on prostate carcinogenesis

Dean

Nelson

2008

Br J Cancer

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Experimental evidence suggests that ageing-associated alterations in the tissue microenvironment act to promote prostate carcinogenesis. In this review, we survey the cellular state of senescence, review its causes, and describe associations with ageing and cancer. We further discuss senescent stromal gene expression changes, which may mediate these effects, and that may serve as therapeutic targets.

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“…TAMs play a central role in many tumor-stromal interactions including angiogenesis, extracellular matrix remodeling, and invasion/metastasis (21,24,25). The degree of macrophage infiltration into human non-small cell lung cancers is correlated with the microvessel counts and inversely correlated with survival (21).…”

Section: Introductionmentioning

confidence: 99%

A Macrophage Gene Expression Signature Defines a Field Effect in the Lung Tumor Microenvironment

et al. 2008

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One area of intensive investigation is to understand complex cellular and signaling interactions in the tumor microenvironment. Using a novel, although straightforward, microarray approach, we defined a gene expression signature from the lung tumor microenvironment in the murine A/J-urethane model of human lung adenocarcinoma. The tumor microenvironment is reflected by the composition of the cell types present and alterations in mRNA levels, resulting in a ''Field Effect'' around the tumor. The genes composing the Field Effect expression signature include proteases and their inhibitors, inflammation markers, and immune signaling molecules. By several criteria, the Field Effect expression signature can be attributed to the macrophage lineage, suggesting a qualitative change in the expression pattern of tumor-associated macrophages (TAM) observed in lung tumors. The protein expression levels for a number of Field Effect genes were verified by Western blot analysis of lung homogenates, and for their expression in macrophages and parenchymal cells outside of the tumors by immunohistochemistry. In addition, the Field Effect expression signature was used to classify bronchoalveolar lavage (BAL) cells from tumor-bearing or age-matched control mice. Using a variety of statistical measures, the Field Effect expression signature correctly classified the BAL cells >94% of the time. Finally, the protein levels for several Field Effect genes were higher in cellfree BAL fluid, indicating they may be secreted by the TAMs. This work suggests that TAMs generate a unique gene expression signature within the tumor microenvironment, and this signature could potentially be used for identifying lung cancer from BAL cells and/or fluid. [Cancer Res 2008;68(1):34-43]

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Role of tumor-associated macrophages in tumor progression and invasion

Cited by 782 publications

References 76 publications

The lymphocyte/monocyte ratio predicts poor clinical outcome and improves the predictive accuracy in patients with soft tissue sarcomas

The lymphocyte/monocyte ratio predicts poor clinical outcome and improves the predictive accuracy in patients with soft tissue sarcomas

Profiling influences of senescent and aged fibroblasts on prostate carcinogenesis

A Macrophage Gene Expression Signature Defines a Field Effect in the Lung Tumor Microenvironment

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