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PMID: 22313874 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Review

Cross-talk between myeloid-derived suppressor cells (MDSC), macrophages, and dendritic cells enhances tumor-induced immune suppression.

Seminars in cancer biology ·Vol. 22 ·No. 4 ·2012-08-00 ·Pages 275-81

Ostrand-Rosenberg S, Sinha P, Beury DW, Clements VK

Abstract

The tumor microenvironment is a complex milieu of tumor and host cells. Host cells can include tumor-reactive T cells capable of killing tumor cells. However, more frequently the tumor and host components interact to generate a highly immune suppressive environment that frustrates T cell cytotoxicity and promotes tumor progression through a variety of immune and non-immune mechanisms. Myeloid-derived suppressor cells (MDSC) are a major host component contributing to the immune suppressive environment. In addition to their inherent immune suppressive function, MDSC amplify the immune suppressive activity of macrophages and dendritic cells via cross-talk. This article will review the cell-cell interactions used by MDSC to inhibit anti-tumor immunity and promote progression, and the role of inflammation in promoting cross-talk between MDSC and other cells in the tumor microenvironment.

MeSH Terms
Animals Dendritic Cells/immunology,metabolism Humans Immunotherapy Inflammation Inflammation Mediators/metabolism Macrophages/immunology,metabolism Myeloid Cells/immunology,metabolism Neoplasms/immunology,pathology,therapy Tumor Escape Tumor Microenvironment/immunology
Chemicals
Inflammation Mediators
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Ostrand-Rosenberg Suzanne
University of Maryland Baltimore County, Department of Biological Sciences, Baltimore, MD 21250, United States. [email protected]
Sinha Pratima
Beury Daniel W
Clements Virginia K
References (70)
70 references, click to expand
  1. Cooperative induction of a tolerogenic dendritic cell phenotype by cytokines secreted by pancreatic carcinoma cells.
    J Immunol. 2006 Sep 1;177(5):3448-60 PMID: 16920987
  2. CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages.
    Cancer Cell. 2009 Aug 4;16(2):91-102 PMID: 19647220
  3. Myeloid suppressor lines inhibit T cell responses by an NO-dependent mechanism.
    J Immunol. 2002 Jan 15;168(2):689-95 PMID: 11777962
  4. A distinct macrophage population mediates metastatic breast cancer cell extravasation, establishment and growth.
    PLoS One. 2009 Aug 10;4(8):e6562 PMID: 19668347
  5. Myeloid-derived suppressor cell activation by combined LPS and IFN-gamma treatment impairs DC development.
    Eur J Immunol. 2009 Oct;39(10):2865-76 PMID: 19637228
  6. Up-regulated myeloid-derived suppressor cell contributes to hepatocellular carcinoma development by impairing dendritic cell function.
    Scand J Gastroenterol. 2011 Feb;46(2):156-64 PMID: 20822377
  7. Trial watch: ipilimumab success in melanoma provides boost for cancer immunotherapy.
    Nat Rev Drug Discov. 2010 Aug;9(8):584 PMID: 20671754
  8. Macrophages regulate the angiogenic switch in a mouse model of breast cancer.
    Cancer Res. 2006 Dec 1;66(23):11238-46 PMID: 17114237
  9. Myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor.
    Hepatology. 2009 Sep;50(3):799-807 PMID: 19551844
  10. Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response.
    J Immunol. 2007 Jul 15;179(2):977-83 PMID: 17617589
  11. Arginase I production in the tumor microenvironment by mature myeloid cells inhibits T-cell receptor expression and antigen-specific T-cell responses.
    Cancer Res. 2004 Aug 15;64(16):5839-49 PMID: 15313928
  12. Myeloid-derived suppressor cells impair the quality of dendritic cell vaccines.
    Cancer Immunol Immunother. 2012 Jun;61(6):827-38 PMID: 22080405
  13. IL-23 suppresses innate immune response independently of IL-17A during carcinogenesis and metastasis.
    Proc Natl Acad Sci U S A. 2010 May 4;107(18):8328-33 PMID: 20404142
  14. Mononuclear myeloid-derived "suppressor" cells express RAE-1 and activate natural killer cells.
    Blood. 2008 Nov 15;112(10):4080-9 PMID: 18753637
  15. Dendritic cells regulate exposure of MHC class II at their plasma membrane by oligoubiquitination.
    Immunity. 2006 Dec;25(6):885-94 PMID: 17174123
  16. Gr-1+CD115+ immature myeloid suppressor cells mediate the development of tumor-induced T regulatory cells and T-cell anergy in tumor-bearing host.
    Cancer Res. 2006 Jan 15;66(2):1123-31 PMID: 16424049
  17. IL-23 promotes tumour incidence and growth.
    Nature. 2006 Jul 27;442(7101):461-5 PMID: 16688182
  18. Prostaglandin E2 promotes tumor progression by inducing myeloid-derived suppressor cells.
    Cancer Res. 2007 May 1;67(9):4507-13 PMID: 17483367
  19. Reduced inflammation in the tumor microenvironment delays the accumulation of myeloid-derived suppressor cells and limits tumor progression.
    Cancer Res. 2007 Oct 15;67(20):10019-26 PMID: 17942936
  20. Dendritic cell dysfunction in cancer: a mechanism for immunosuppression.
    Immunol Cell Biol. 2005 Oct;83(5):451-61 PMID: 16174093
  21. Dendritic cells infiltrating human non-small cell lung cancer are blocked at immature stage.
    J Immunol. 2007 Mar 1;178(5):2763-9 PMID: 17312119
  22. A nonclassical non-Valpha14Jalpha18 CD1d-restricted (type II) NKT cell is sufficient for down-regulation of tumor immunosurveillance.
    J Exp Med. 2005 Dec 19;202(12):1627-33 PMID: 16365146
  23. Proinflammatory S100 proteins regulate the accumulation of myeloid-derived suppressor cells.
    J Immunol. 2008 Oct 1;181(7):4666-75 PMID: 18802069
  24. Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer.
    Nat Med. 2007 Jul;13(7):828-35 PMID: 17603493
  25. Inflammation induces myeloid-derived suppressor cells that facilitate tumor progression.
    J Immunol. 2006 Jan 1;176(1):284-90 PMID: 16365420
  26. Improved survival with ipilimumab in patients with metastatic melanoma.
    N Engl J Med. 2010 Aug 19;363(8):711-23 PMID: 20525992
  27. Inhibition of dendritic cell differentiation and accumulation of myeloid-derived suppressor cells in cancer is regulated by S100A9 protein.
    J Exp Med. 2008 Sep 29;205(10):2235-49 PMID: 18809714
  28. Immune stimulatory receptor CD40 is required for T-cell suppression and T regulatory cell activation mediated by myeloid-derived suppressor cells in cancer.
    Cancer Res. 2010 Jan 1;70(1):99-108 PMID: 19996287
  29. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation.
    J Exp Med. 2005 Jan 17;201(2):233-40 PMID: 15657292
  30. Interleukin (IL) 1beta induction of IL-6 is mediated by a novel phosphatidylinositol 3-kinase-dependent AKT/IkappaB kinase alpha pathway targeting activator protein-1.
    J Biol Chem. 2008 Sep 19;283(38):25900-12 PMID: 18515365
  31. Gemcitabine selectively eliminates splenic Gr-1+/CD11b+ myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity.
    Clin Cancer Res. 2005 Sep 15;11(18):6713-21 PMID: 16166452
  32. Chemokine nitration prevents intratumoral infiltration of antigen-specific T cells.
    J Exp Med. 2011 Sep 26;208(10):1949-62 PMID: 21930770
  33. Exploring the full spectrum of macrophage activation.
    Nat Rev Immunol. 2008 Dec;8(12):958-69 PMID: 19029990
  34. Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes.
    Cancer Res. 2010 Jul 15;70(14):5728-39 PMID: 20570887
  35. Tumor-associated macrophages and the related myeloid-derived suppressor cells as a paradigm of the diversity of macrophage activation.
    Hum Immunol. 2009 May;70(5):325-30 PMID: 19236898
  36. Direct ex vivo analysis of dendritic cells in patients with hepatocellular carcinoma.
    World J Gastroenterol. 2006 May 28;12(20):3275-82 PMID: 16718852
  37. Expansion of spleen myeloid suppressor cells represses NK cell cytotoxicity in tumor-bearing host.
    Blood. 2007 May 15;109(10):4336-42 PMID: 17244679
  38. Mechanism of T cell tolerance induced by myeloid-derived suppressor cells.
    J Immunol. 2010 Mar 15;184(6):3106-16 PMID: 20142361
  39. Mechanisms and functional significance of tumour-induced dendritic-cell defects.
    Nat Rev Immunol. 2004 Dec;4(12):941-52 PMID: 15573129
  40. CD11b+/Gr-1+ immature myeloid cells mediate suppression of T cells in mice bearing tumors of IL-1beta-secreting cells.
    J Immunol. 2005 Dec 15;175(12):8200-8 PMID: 16339559
  41. TCR zeta down-regulation under chronic inflammation is mediated by myeloid suppressor cells differentially distributed between various lymphatic organs.
    J Immunol. 2006 Oct 1;177(7):4763-72 PMID: 16982917
  42. Understanding the IL-23-IL-17 immune pathway.
    Trends Immunol. 2006 Jan;27(1):17-23 PMID: 16290228
  43. Myeloid-derived suppressor cells down-regulate L-selectin expression on CD4+ and CD8+ T cells.
    J Immunol. 2009 Jul 15;183(2):937-44 PMID: 19553533
  44. Myeloid-derived suppressor cells inhibit T-cell activation by depleting cystine and cysteine.
    Cancer Res. 2010 Jan 1;70(1):68-77 PMID: 20028852
  45. Reduction of myeloid-derived suppressor cells and induction of M1 macrophages facilitate the rejection of established metastatic disease.
    J Immunol. 2005 Jan 15;174(2):636-45 PMID: 15634881
  46. Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis.
    Cancer Cell. 2004 Oct;6(4):409-21 PMID: 15488763
  47. IL-1β regulates a novel myeloid-derived suppressor cell subset that impairs NK cell development and function.
    Eur J Immunol. 2010 Dec;40(12):3347-57 PMID: 21110318
  48. Inhibition of early tumor growth requires J alpha 18-positive (natural killer T) cells.
    Cancer Res. 2003 Jun 15;63(12):3058-60 PMID: 12810627
  49. Smoldering and polarized inflammation in the initiation and promotion of malignant disease.
    Cancer Cell. 2005 Mar;7(3):211-7 PMID: 15766659
  50. Deficiencies in myeloid antigen-presenting cells in women with cervical squamous intraepithelial lesions.
    Cancer. 2006 Sep 1;107(5):999-1007 PMID: 16874820
  51. Myeloid-derived suppressor cells: linking inflammation and cancer.
    J Immunol. 2009 Apr 15;182(8):4499-506 PMID: 19342621
  52. Developmental pathways that generate natural-killer-cell diversity in mice and humans.
    Nat Rev Immunol. 2007 Sep;7(9):703-14 PMID: 17717540
  53. Macrophages are an abundant component of myeloma microenvironment and protect myeloma cells from chemotherapy drug-induced apoptosis.
    Blood. 2009 Oct 22;114(17):3625-8 PMID: 19710503
  54. 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 Dec 1;198(11):1741-52 PMID: 14657224
  55. Role of the mTOR pathway in LPS-activated monocytes: influence of hypertonic saline.
    J Surg Res. 2011 Dec;171(2):769-76 PMID: 20828737
  56. Differential regulation of IL-12 and IL-10 gene expression in macrophages by the basic leucine zipper transcription factor c-Maf fibrosarcoma.
    J Immunol. 2002 Nov 15;169(10):5715-25 PMID: 12421951
  57. Surface expression of MHC class II in dendritic cells is controlled by regulated ubiquitination.
    Nature. 2006 Nov 2;444(7115):115-8 PMID: 17051151
  58. Antigen-specific inhibition of CD8+ T cell response by immature myeloid cells in cancer is mediated by reactive oxygen species.
    J Immunol. 2004 Jan 15;172(2):989-99 PMID: 14707072
  59. Tumor-infiltrating myeloid cells induce tumor cell resistance to cytotoxic T cells in mice.
    J Clin Invest. 2011 Oct;121(10):4015-29 PMID: 21911941
  60. Inflammation enhances myeloid-derived suppressor cell cross-talk by signaling through Toll-like receptor 4.
    J Leukoc Biol. 2009 Jun;85(6):996-1004 PMID: 19261929
  61. Interleukin-10-induced MARCH1 mediates intracellular sequestration of MHC class II in monocytes.
    Eur J Immunol. 2008 May;38(5):1225-30 PMID: 18389477
  62. Mammalian target of rapamycin and glycogen synthase kinase 3 differentially regulate lipopolysaccharide-induced interleukin-12 production in dendritic cells.
    Blood. 2008 Aug 1;112(3):635-43 PMID: 18492954
  63. Myeloid-derived suppressor cells promote cross-tolerance in B-cell lymphoma by expanding regulatory T cells.
    Cancer Res. 2008 Jul 1;68(13):5439-49 PMID: 18593947
  64. Interleukin 10 acts on regulatory T cells to maintain expression of the transcription factor Foxp3 and suppressive function in mice with colitis.
    Nat Immunol. 2009 Nov;10(11):1178-84 PMID: 19783988
  65. Rapamycin enhances LPS induction of tissue factor and tumor necrosis factor-alpha expression in macrophages by reducing IL-10 expression.
    Mol Immunol. 2009 Jul;46(11-12):2249-55 PMID: 19447494
  66. Numerical and functional defects of blood dendritic cells in early- and late-stage breast cancer.
    Br J Cancer. 2007 Nov 5;97(9):1251-9 PMID: 17923873
  67. Lipopolysaccharide induces physical proximity between CD14 and toll-like receptor 4 (TLR4) prior to nuclear translocation of NF-kappa B.
    J Immunol. 2000 Oct 1;165(7):3541-4 PMID: 11034352
  68. Cancer-expanded myeloid-derived suppressor cells induce anergy of NK cells through membrane-bound TGF-beta 1.
    J Immunol. 2009 Jan 1;182(1):240-9 PMID: 19109155
  69. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates.
    J Clin Oncol. 2010 Jul 1;28(19):3167-75 PMID: 20516446
  70. Coordinated regulation of myeloid cells by tumours.
    Nat Rev Immunol. 2012 Mar 22;12(4):253-68 PMID: 22437938
Article Info
Journal
Seminars in cancer biology
Abbr.
Semin Cancer Biol
ISSN
1096-3650
DOI
10.1016/j.semcancer.2012.01.011
Email
[email protected]
Published
2012-08-00
Epub
2012-00-01
Pages
275-81
Language
English
Region
England
NLM ID
9010218
PMCID
PMC3701942
Subset
IM
Grants
NCI NIH HHS · R01 CA084232 · United States
NCI NIH HHS · R01 CA115880 · United States
NCI NIH HHS · R01CA115880 · United States
NCI NIH HHS · R01CA84232 · United States
External Links
PubMed source DOI: 10.1016/j.semcancer.2012.01.011 PMC Full Text View journal details
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