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Vascular Cell
Published in: Vascular Cell 1/2012

Open Access 01-12-2012 | Review

Myeloid cells in tumor inflammation

Authors: Michael C Schmid, Judith A Varner

Published in: Vascular Cell | Issue 1/2012

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Abstract

Bone marrow derived myeloid cells progressively accumulate in tumors, where they establish an inflammatory microenvironment that is favorable for tumor growth and spread. These cells are comprised primarily of monocytic and granulocytic myeloid derived suppressor cells (MDSCs) or tumor-associated macrophages (TAMs), which are generally associated with a poor clinical outcome. MDSCs and TAMs promote tumor progression by stimulating immunosuppression, neovascularization, metastasis and resistance to anti-cancer therapy. Strategies to target the tumor-promoting functions of myeloid cells could provide substantial therapeutic benefit to cancer patients.
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Literature
1.
Biswas SK, Mantovani A: Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol. 2010, 11 (10): 889-896. 10.1038/ni.1937.CrossRefPubMed
2.
3.
4.
5.
Mantovani A, et al: Cancer-related inflammation. Nature. 2008, 454 (7203): 436-444. 10.1038/nature07205.CrossRefPubMed
6.
Mantovani A, Sica A: Macrophages, innate immunity and cancer: balance, tolerance, and diversity. Curr Opin Immunol. 2010, 22 (2): 231-237. 10.1016/j.coi.2010.01.009.CrossRefPubMed
7.
Hanahan D, Coussens LM: Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell. 2012, 21 (3): 309-322. 10.1016/j.ccr.2012.02.022.CrossRefPubMed
8.
Gabrilovich DI, Ostrand-Rosenberg S, Bronte V: Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol. 2012, 12 (4): 253-268. 10.1038/nri3175.PubMedCentralCrossRefPubMed
9.
10.
11.
Gordon S, Martinez FO: Alternative activation of macrophages: mechanism and functions. Immunity. 2010, 32 (5): 593-604. 10.1016/j.immuni.2010.05.007.CrossRefPubMed
12.
Greten FR, et al: IKKbeta links inflammation and tumorigenesis in a mouse model of colitis-associated cancer. Cell. 2004, 118 (3): 285-296. 10.1016/j.cell.2004.07.013.CrossRefPubMed
13.
Karin M, Greten FR: NF-kappaB: linking inflammation and immunity to cancer development and progression. Nat Rev Immunol. 2005, 5 (10): 749-759. 10.1038/nri1703.CrossRefPubMed
14.
Lin EY, et al: Macrophages regulate the angiogenic switch in a mouse model of breast cancer. Cancer Res. 2006, 66 (23): 11238-11246. 10.1158/0008-5472.CAN-06-1278.CrossRefPubMed
15.
Qian B, et al: A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth. PLoS One. 2009, 4 (8): e6562-10.1371/journal.pone.0006562.PubMedCentralCrossRefPubMed
16.
Ruffell B, Affara NI, Coussens LM: Differential macrophage programming in the tumor microenvironment. Trends Immunol. 2012, 33 (3): 119-126. 10.1016/j.it.2011.12.001.PubMedCentralCrossRefPubMed
17.
Qian BZ, Pollard JW: Macrophage diversity enhances tumor progression and metastasis. Cell. 2010, 141 (1): 39-51. 10.1016/j.cell.2010.03.014.CrossRefPubMed
18.
Rolny C, et al: HRG inhibits tumor growth and metastasis by inducing macrophage polarization and vessel normalization through downregulation of PlGF. Cancer Cell. 2011, 19 (1): 31-44. 10.1016/j.ccr.2010.11.009.CrossRefPubMed
19.
Peranzoni E, et al: Myeloid-derived suppressor cell heterogeneity and subset definition. Curr Opin Immunol. 2010, 22 (2): 238-244. 10.1016/j.coi.2010.01.021.CrossRefPubMed
20.
Bronte V, et al: Identification of a CD11b(+)/Gr-1(+)/CD31(+) myeloid progenitor capable of activating or suppressing CD8(+) T cells. Blood. 2000, 96 (12): 3838-3846.PubMedCentralPubMed
21.
Mandruzzato S, et al: IL4Ralpha + myeloid-derived suppressor cell expansion in cancer patients. J Immunol. 2009, 182 (10): 6562-6568. 10.4049/jimmunol.0803831.CrossRefPubMed
22.
Corzo CA, et al: HIF-1alpha regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment. J Exp Med. 2010, 207 (11): 2439-2453. 10.1084/jem.20100587.PubMedCentralCrossRefPubMed
23.
Corzo CA, et al: Mechanism regulating reactive oxygen species in tumor-induced myeloid-derived suppressor cells. J Immunol. 2009, 182 (9): 5693-5701. 10.4049/jimmunol.0900092.PubMedCentralCrossRefPubMed
24.
Diaz-Montero CM, et al: Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother. 2009, 58 (1): 49-59. 10.1007/s00262-008-0523-4.PubMedCentralCrossRefPubMed
25.
Movahedi K, et al: Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell-suppressive activity. Blood. 2008, 111 (8): 4233-4244. 10.1182/blood-2007-07-099226.CrossRefPubMed
26.
Yang R, et al: CD80 in immune suppression by mouse ovarian carcinoma-associated Gr-1 + CD11b + myeloid cells. Cancer Res. 2006, 66 (13): 6807-6815. 10.1158/0008-5472.CAN-05-3755.CrossRefPubMed
27.
Gallina G, et al: Tumors induce a subset of inflammatory monocytes with immunosuppressive activity on CD8+ T cells. J Clin Invest. 2006, 116 (10): 2777-2790. 10.1172/JCI28828.PubMedCentralCrossRefPubMed
28.
Sawanobori Y, et al: Chemokine-mediated rapid turnover of myeloid-derived suppressor cells in tumor-bearing mice. Blood. 2008, 111 (12): 5457-5466. 10.1182/blood-2008-01-136895.CrossRefPubMed
29.
30.
Haile LA, et al: CD49d is a new marker for distinct myeloid-derived suppressor cell subpopulations in mice. J Immunol. 2010, 185 (1): 203-210. 10.4049/jimmunol.0903573.CrossRefPubMed
31.
Van Ginderachter JA, et al: Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands reverse CTL suppression by alternatively activated (M2) macrophages in cancer. Blood. 2006, 108 (2): 525-535. 10.1182/blood-2005-09-3777.CrossRefPubMed
32.
Almand B, et al: Increased production of immature myeloid cells in cancer patients: a mechanism of immunosuppression in cancer. J Immunol. 2001, 166 (1): 678-689.CrossRefPubMed
33.
Ochoa AC, et al: Arginase, prostaglandins, and myeloid-derived suppressor cells in renal cell carcinoma. Clin Cancer Res. 2007, 13 (2 Pt 2): 721s-726s.CrossRefPubMed
34.
Filipazzi P, et al: Identification of a new subset of myeloid suppressor cells in peripheral blood of melanoma patients with modulation by a granulocyte-macrophage colony-stimulation factor-based antitumor vaccine. J Clin Oncol. 2007, 25 (18): 2546-2553. 10.1200/JCO.2006.08.5829.CrossRefPubMed
35.
Hoechst B, et al: A new population of myeloid-derived suppressor cells in hepatocellular carcinoma patients induces CD4(+)CD25(+)Foxp3(+) T cells. Gastroenterology. 2008, 135 (1): 234-243. 10.1053/j.gastro.2008.03.020.CrossRefPubMed
36.
Vuk-Pavlovic S, et al: Immunosuppressive CD14 + HLA-DRlow/- monocytes in prostate cancer. Prostate. 2010, 70 (4): 443-455.PubMedCentralPubMed
37.
Solito S, et al: A human promyelocytic-like population is responsible for the immune suppression mediated by myeloid-derived suppressor cells. Blood. 2011, 118 (8): 2254-2265. 10.1182/blood-2010-12-325753.PubMedCentralCrossRefPubMed
38.
Luster AD, Alon R, von Andrian UH: Immune cell migration in inflammation: present and future therapeutic targets. Nat Immunol. 2005, 6 (12): 1182-1190. 10.1038/ni1275.CrossRefPubMed
39.
Weber C, Koenen RR: Fine-tuning leukocyte responses: towards a chemokine’interactome’. Trends Immunol. 2006, 27 (6): 268-273. 10.1016/j.it.2006.04.002.CrossRefPubMed
40.
Du R, et al: HIF1alpha induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion. Cancer Cell. 2008, 13 (3): 206-220. 10.1016/j.ccr.2008.01.034.PubMedCentralCrossRefPubMed
41.
Nakasone ES, et al: Imaging tumor-stroma interactions during chemotherapy reveals contributions of the microenvironment to resistance. Cancer Cell. 2012, 21 (4): 488-503. 10.1016/j.ccr.2012.02.017.PubMedCentralCrossRefPubMed
42.
Schmid MC, et al: Combined blockade of integrin-alpha4beta1 plus cytokines SDF-1alpha or IL-1beta potently inhibits tumor inflammation and growth. Cancer Res. 2011, 71 (22): 6965-6975. 10.1158/0008-5472.CAN-11-0588.PubMedCentralCrossRefPubMed
43.
Yang L, et al: Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1 + CD11b + myeloid cells that promote metastasis. Cancer Cell. 2008, 13 (1): 23-35. 10.1016/j.ccr.2007.12.004.PubMedCentralCrossRefPubMed
44.
Wang XQ, et al: The high level of RANTES in the ectopic milieu recruits macrophages and induces their tolerance in progression of endometriosis. J Mol Endocrinol. 2010, 45 (5): 291-299. 10.1677/JME-09-0177.CrossRefPubMed
45.
Shojaei F, et al: G-CSF-initiated myeloid cell mobilization and angiogenesis mediate tumor refractoriness to anti-VEGF therapy in mouse models. Proc Natl Acad Sci U S A. 2009, 106 (16): 6742-6747. 10.1073/pnas.0902280106.PubMedCentralCrossRefPubMed
46.
Shojaei F, et al: Bv8 regulates myeloid-cell-dependent tumour angiogenesis. Nature. 2007, 450 (7171): 825-831. 10.1038/nature06348.CrossRefPubMed
47.
Denardo DG, et al: Leukocyte Complexity Predicts Breast Cancer Survival and Functionally Regulates Response to Chemotherapy. Cancer Discov. 2011, 1: 54-67. 10.1158/2159-8274.CD-10-0028.PubMedCentralCrossRefPubMed
48.
49.
50.
Ley K, et al: Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol. 2007, 7 (9): 678-689. 10.1038/nri2156.CrossRefPubMed
51.
Schmid MC, et al: Receptor tyrosine kinases and TLR/IL1Rs unexpectedly activate myeloid cell PI3kgamma, a single convergent point promoting tumor inflammation and progression. Cancer Cell. 2011, 19 (6): 715-727. 10.1016/j.ccr.2011.04.016.PubMedCentralCrossRefPubMed
52.
53.
Desgrosellier JS, Cheresh DA: Integrins in cancer: biological implications and therapeutic opportunities. Nat Rev Cancer. 2010, 10 (1): 9-22. 10.1038/nrc2748.PubMedCentralCrossRefPubMed
54.
Foubert P, Varner JA: Integrins in tumor angiogenesis and lymphangiogenesis. Methods Mol Biol. 2012, 757: 471-486.CrossRefPubMed
55.
Jin H, et al: Integrin alpha4beta1 promotes monocyte trafficking and angiogenesis in tumors. Cancer Res. 2006, 66 (4): 2146-2152. 10.1158/0008-5472.CAN-05-2704.CrossRefPubMed
56.
Luque A, et al: Activated conformations of very late activation integrins detected by a group of antibodies (HUTS) specific for a novel regulatory region (355–425) of the common beta 1 chain. J Biol Chem. 1996, 271 (19): 11067-11075. 10.1074/jbc.271.19.11067.CrossRefPubMed
57.
Arnaout MA, Mahalingam B, Xiong JP: Integrin structure, allostery, and bidirectional signaling. Annu Rev Cell Dev Biol. 2005, 21: 381-410. 10.1146/annurev.cellbio.21.090704.151217.CrossRefPubMed
58.
59.
60.
Feral CC, et al: Blocking the alpha 4 integrin-paxillin interaction selectively impairs mononuclear leukocyte recruitment to an inflammatory site. J Clin Invest. 2006, 116 (3): 715-723. 10.1172/JCI26091.PubMedCentralCrossRefPubMed
61.
Manevich E, et al: Talin 1 and paxillin facilitate distinct steps in rapid VLA-4-mediated adhesion strengthening to vascular cell adhesion molecule 1. J Biol Chem. 2007, 282 (35): 25338-25348. 10.1074/jbc.M700089200.CrossRefPubMed
62.
Lewis JS, et al: Expression of vascular endothelial growth factor by macrophages is up-regulated in poorly vascularized areas of breast carcinomas. J Pathol. 2000, 192 (2): 150-158. 10.1002/1096-9896(2000)9999:9999<::AID-PATH687>3.0.CO;2-G.CrossRefPubMed
63.
Sunderkotter C, et al: Macrophages and angiogenesis. J Leukoc Biol. 1994, 55 (3): 410-422.PubMed
64.
Giraudo E, Inoue M, Hanahan D: An amino-bisphosphonate targets MMP-9-expressing macrophages and angiogenesis to impair cervical carcinogenesis. J Clin Invest. 2004, 114 (5): 623-633.PubMedCentralCrossRefPubMed
65.
66.
Esposito I, et al: Inflammatory cells contribute to the generation of an angiogenic phenotype in pancreatic ductal adenocarcinoma. J Clin Pathol. 2004, 57 (6): 630-636. 10.1136/jcp.2003.014498.PubMedCentralCrossRefPubMed
67.
Huang S, et al: Contributions of stromal metalloproteinase-9 to angiogenesis and growth of human ovarian carcinoma in mice. J Natl Cancer Inst. 2002, 94 (15): 1134-1142. 10.1093/jnci/94.15.1134.CrossRefPubMed
68.
Ostrand-Rosenberg S, Sinha P: Myeloid-derived suppressor cells: linking inflammation and cancer. J Immunol. 2009, 182 (8): 4499-4506. 10.4049/jimmunol.0802740.PubMedCentralCrossRefPubMed
69.
70.
Rodriguez PC, et al: L-arginine consumption by macrophages modulates the expression of CD3 zeta chain in T lymphocytes. J Immunol. 2003, 171 (3): 1232-1239.CrossRefPubMed
71.
72.
Sauer H, Wartenberg M, Hescheler J: Reactive oxygen species as intracellular messengers during cell growth and differentiation. Cell Physiol Biochem. 2001, 11 (4): 173-186. 10.1159/000047804.CrossRefPubMed
73.
Fichtner-Feigl S, et al: Restoration of tumor immunosurveillance via targeting of interleukin-13 receptor-alpha 2. Cancer Res. 2008, 68 (9): 3467-3475. 10.1158/0008-5472.CAN-07-5301.PubMedCentralCrossRefPubMed
74.
Terabe M, et al: Transforming growth factor-beta production and myeloid cells are an effector mechanism through which CD1d-restricted T cells block cytotoxic T lymphocyte-mediated tumor immunosurveillance: abrogation prevents tumor recurrence. J Exp Med. 2003, 198 (11): 1741-1752. 10.1084/jem.20022227.PubMedCentralCrossRefPubMed
75.
Shojaei F, et al: Tumor refractoriness to anti-VEGF treatment is mediated by CD11b + Gr1+ myeloid cells. Nat Biotechnol. 2007, 25 (8): 911-920. 10.1038/nbt1323.CrossRefPubMed
76.
Qu X, et al: Induction of Bv8 expression by granulocyte-colony stimulating factor in CD11b + Gr1+ cells: Key role of Stat3 signaling. J Biol Chem. 2012, 287 (23): 19574-19584. 10.1074/jbc.M111.326801.PubMedCentralCrossRefPubMed
77.
Shojaei F, et al: Role of Bv8 in neutrophil-dependent angiogenesis in a transgenic model of cancer progression. Proc Natl Acad Sci U S A. 2008, 105 (7): 2640-2645. 10.1073/pnas.0712185105.PubMedCentralCrossRefPubMed
78.
Jain RK: Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science. 2005, 307 (5706): 58-62. 10.1126/science.1104819.CrossRefPubMed
79.
Mazzieri R, et al: Targeting the ANG2/TIE2 axis inhibits tumor growth and metastasis by impairing angiogenesis and disabling rebounds of proangiogenic myeloid cells. Cancer Cell. 2011, 19 (4): 512-526. 10.1016/j.ccr.2011.02.005.CrossRefPubMed
80.
Stockmann C, et al: Deletion of vascular endothelial growth factor in myeloid cells accelerates tumorigenesis. Nature. 2008, 456 (7223): 814-818. 10.1038/nature07445.PubMedCentralCrossRefPubMed
81.
Shree T, et al: Macrophages and cathepsin proteases blunt chemotherapeutic response in breast cancer. Genes Dev. 2011, 25 (23): 2465-2479. 10.1101/gad.180331.111.PubMedCentralCrossRefPubMed
82.
Squadrito ML, et al: miR-511-3p Modulates Gentic Programs of Tumor-Associated Macrophages. Cell Reports. 2012, 1: 141-154. 10.1016/j.celrep.2011.12.005.CrossRefPubMed
83.
DeNardo DG, et al: CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell. 2009, 16 (2): 91-102. 10.1016/j.ccr.2009.06.018.PubMedCentralCrossRefPubMed
Metadata
Title
Myeloid cells in tumor inflammation
Authors
Michael C Schmid
Judith A Varner
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Vascular Cell / Issue 1/2012
Electronic ISSN: 2045-824X
DOI
https://doi.org/10.1186/2045-824X-4-14

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Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

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Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

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