Tie2-expressing monocytes: regulation of tumor angiogenesis and therapeutic implications

Palma, Michele De; Murdoch, Craig; Venneri, Mary Anna; Naldini, Luigi; Lewis, Claire E.

doi:10.1016/j.it.2007.09.004

Cited by 247 publications

(234 citation statements)

References 46 publications

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“…Strategies include interference with the M-CSF axis [13] or chemokine expression/function (in particular CCL2, e.g. [13,15]), or depletion of angiogenic monocyte subsets [48,49]. Moreover, the influence of selected chemotherapeutic agents on the viability and function of myelomonocytic cells may contribute to or be a critical component of the agents' anti-tumor activity [9,50,51].…”

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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“…In vivo counterparts of M2 macrophage polarization have been observed in tissue remodelling during ontogenesis [28], chronic inflammation [29][30][31][32][33][34][35][36][37][38][39][40][41][42], cancer [9,12,16,17], bacterial [43][44][45][46][47][48][49] and parasitic [50][51][52][53] infections. Evidence has also accumulated that polarized macrophages are more than mere spectators of immunopathology [35][36][37][38][39][40][41][50][51][52].…”

Section: Activation and Adaptive Responses Of Macrophagesmentioning

confidence: 99%

“…Fourth, the relationship between polarized macrophages and monocyte subsets remains unclear [54]. For instance, functional and profiling data suggest a similarity between the Tie2 + monocytes and M2-polarized macrophages [12], but that does not imply a continuum of differentiation. In general, the plasticity of mononuclear phagocytes in response to environmental signals highlights how, in fact, innate responses have a prominent adaptive component [55].…”

Section: Activation and Adaptive Responses Of Macrophagesmentioning

confidence: 99%

“…The issue of lineage of the actual effectors of MDSC-mediated suppression is even more relevant when their recruitment and activation in non-lymphoid tissues is considered. For instance, do MDSC retain an immature phenotype in tumour tissues or do they differentiate into tumourassociated macrophages [9][10][11] [9,12,16,17], bacterial [43][44][45][46][47][48][49] and parasitic [50][51][52][53] infections. Evidence has also accumulated that polarized macrophages are more than mere spectators of immunopathology [35][36][37][38][39][40][41][50][51][52].…”

Section: Introductionmentioning

confidence: 99%

“…For instance, do MDSC retain an immature phenotype in tumour tissues or do they differentiate into tumourassociated macrophages [9][10][11]? How do MDSC relate to monocyte and macrophage subsets or differentiation stages, such as the Tie2 + monocytes [12], tumour-associated macrophages Commentary and, more generally, polarized M2 macrophages [13]? Limited profiling data on conventional MDSC suggest a definite relationship with polarized M2 cells [14,15].…”

Section: Introductionmentioning

confidence: 99%

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From phagocyte diversity and activation to probiotics: Back to Metchnikoff

Mantovani

2008

Eur J Immunol

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In this issue of the European Journal of Immunology, Siamon Gordon gives a detailed account of Metchnikoff's life and his achievements (Eur. J. Immunol. 2008. 38: 3257-3264). Looking back at the roots of innate immunity stimulates reflections on open issues in the field. Here, I give a personal view of some of these issues, including myeloid-derived suppressor cells, macrophage polarization and adaptive responses of mononuclear phagocytes. Key words: Macrophage activation Á Macrophages Á M1/M2 polarization Á Probiotics See accompanying article by Gordon IntroductionIn his scholarly review [1], Siamon Gordon tracks the roots of innate immunity to Elie Metchnikoff. The essay provides a fascinating insight into Metchnikoff's scientific life and how he tackled fundamental issues in science, some of which remain with us to this day. The perspective offered by a major player in the very same field of phagocytes and innate immunity [2,3] adds flavour and fascination to this article not necessarily present in other accounts [4]. Such a reflection on a central part of modern immunology stimulates consideration of remaining open issues and there follows a personal view of some of these.Phagocyte heterogeneity: From microphage-macrophage dichotomy to myeloid-derived suppressor cellsThe fundamental distinction between polymorphonuclear leukocytes (microphages) and mononuclear phagocytes (macrophages) was a major first step in the dissection of phagocyte heterogeneity and lineage differentiation. The identification of myeloid-derived suppressor cells (MDSC) [5][6][7] raises the questions whether the classic sharp distinction between the myeloid and the monocyte-macrophage differentiation and activation pathways is appropriate. In contrast to long-held views, neutrophils express specific transcriptional programmes in response to environmental signals [8]. MDSC include immature myeloid precursors that can further differentiate, and play a key role in the suppression of adaptive immunity in diverse pathological conditions ranging from cancer to chronic infections [5][6][7]. Are we dealing with a blurring of a classic distinction or with a well-defined third phagocyte population? Using current identification and separation criteria (e.g. Gr1, CD11b, F4/80) MDSC in the blood and lymphoid organs are a mixed population, which includes myeloid cells at different stages of differentiation and mononuclear phagocytes. Thus, the definition of MDSC remains an operational one rather than that of a cell type, a reality that is frequently neglected. The issue of lineage of the actual effectors of MDSC-mediated suppression is even more relevant when their recruitment and activation in non-lymphoid tissues is considered. For instance, do MDSC retain an immature phenotype in tumour tissues or do they differentiate into tumourassociated macrophages [9][10][11] [9,12,16,17], bacterial [43][44][45][46][47][48][49] and parasitic [50][51][52][53] infections. Evidence has also accumulated that polarized macrophages are more than mere spectators of i...

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An optimized flow cytometry protocol for analysis of angiogenic monocytes and endothelial progenitor cells in peripheral blood

et al. 2009

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Circulating adult CD341 VEGFR2 1 endothelial progenitor cells (EPCs) have been shown to differentiate into endothelial cells, thus contributing to vascular homeostasis. Furthermore, a subset of circulating CD141 monocytes coexpresses CD16 together with the angiopoietin receptor Tie2 and has been functionally implicated in tumor angiogenesis. However, clinically applicable protocols for flow cytometric quantification of EPCs and Tie2 1 monocytes in peripheral blood and a consensus on reference values remain elusive. The number of Tie2 1 CD14 1 CD16 mid angiogenic monocytes and CD34 1 VEGFR2 1 CD45 low/2 EPCs was assessed in the peripheral venous blood of patients with stable coronary artery disease by three-color flow cytometry using specific monoclonal antibodies conjugated to PerCP, PE, PE-Cy7, APC, and APC-Cy7. Scatter multigating with exclusion of dead cells was performed to dissect complex mononuclear cell populations. This analysis was further refined by matching bright fluorochromes (PE-Cy7, PE, APC) with dimly expressed markers (CD34, VEGFR2, Tie2), by automatic compensation for minimizing fluorescence spillover and by using fluorescence-minus-one (FMO) controls to determine positive/negative boundaries. Presuming a Gaussian distribution, we obtained average values (mean AE SD) of 1.45 AE 1.29% for Tie2 1 CD14 1 CD16 mid monocytes (n ¼ 11, range: 0.12-3.64%) and 0.019 AE 0.013% for CD34low/2 EPCs (n ¼ 17, range: 0.003-0.042%). The intra-and inter-assay variability was 1.6% and 4.5%, respectively. We have optimized a fast and sensitive assay for the flow cytometric quantification of circulating angiogenic monocytes and EPCs in cardiovascular medicine. This protocol may represent a basis for standardized analysis and monitoring of these cell subsets to define their normal range and prognostic/diagnostic value in clinical use. ' 2009 International Society for Advancement of Cytometry

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Tie2-expressing monocytes: regulation of tumor angiogenesis and therapeutic implications

Cited by 247 publications

References 46 publications

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

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

From phagocyte diversity and activation to probiotics: Back to Metchnikoff

An optimized flow cytometry protocol for analysis of angiogenic monocytes and endothelial progenitor cells in peripheral blood

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