, 36:9729 | Cite as

Ageing and myeloid-derived suppressor cells: possible involvement in immunosenescence and age-related disease

  • Valquiria BuenoEmail author
  • Osvaldo Augusto Sant’Anna
  • Janet M Lord


Infections, cancer and autoimmune diseases occur more frequently in the elderly, and although many factors contribute to this, the age-related remodelling of the immune system, termed immunosenescence, plays a major role. Over the last two decades, studies have evaluated the effect of ageing on both the adaptive and innate arms of the immune system and demonstrated compromised function in several cells including lymphocytes (naïve, effector and memory), regulatory T and B cells, monocytes, neutrophils and NK cells. In addition, a well-documented feature of ageing is the increase in systemic inflammatory status (inflammageing), with raised serum levels of IL6, TNFα and CRP as well as reduced IL10. Recently, myeloid-derived suppressor cells have been the focus of many reports as these cells show immunosuppressive properties and are present in higher frequency during infections, cancer and autoimmunity. Importantly, there have been publications showing increased numbers of myeloid-derived suppressor cells in aged mice and humans. In this review, we discuss the current literature on myeloid-derived suppressor cells, their possible role in altered immune function in the elderly, and whether it may be possible to manipulate these cells to alleviate age-related immune dysfunction.


Ageing Immunity Myeloid-derived suppressor cells Infections Cancer Autoimmune diseases 



This work was supported by FAPESP São Paulo Research Foundation (2012/51747-6; 2013/07467-1), National Institute of Science and Technology in Toxins (INCTTOX), Council of Technological and Scientific Development (CNPq)


  1. Akbar AN, Beverly PC, Salmon M (2004) Will telomere erosion lead to a loss of T-cell memory? Nat Rev Immunol 4:737–743PubMedCrossRefGoogle Scholar
  2. Alonso-Arias R, Moro-Garcia MA, López-Vázquez A, Rodrigo L, Baltar J, Garcia FMS, Jaurrieta JJ, López-Larrea C (2011) NKG2D expression in CD4+ T lymphocyte as a marker of senescence in the aged immune system. Age (Dordr) 33:591–605CrossRefGoogle Scholar
  3. Beerman I, Bhattacharya D, Zandi S, Sigvardsson M, Weissman IL, Bryder D, Rossi DJ (2010) Functionally distinct hematopoietic stem cells modulate hematopoietic lineage potential during aging by a mechanism of clonal expansion. Proc Natl Acad Sci U S A 107:5465–5470PubMedCentralPubMedCrossRefGoogle Scholar
  4. Beigel JH (2008) Influenza. Crit Care Med 36(9):2660–2666PubMedCentralPubMedCrossRefGoogle Scholar
  5. Bingisser R, Tilbrook P, Holt P, Kees U (1998) Macrophage-derived nitric oxide regulates T-cell activation via reversible disruption of the Jak3/STAT5 signaling pathway. J Immunol 160:5729–5734PubMedGoogle Scholar
  6. Busch A, Zeh D, Janzen V, Mügge LO, Wolf D, Fingerhut L, Hahn-Ast C, Maurer O, Brossart P, von Lilienfeld-Toal M (2014) Treatment with lenalidomide induces immunoactivating and counter-regulatory immunosuppressive changes in myeloma patients. Clin Exp Immunol 177:439–453PubMedCrossRefGoogle Scholar
  7. Butcher SK, Chahal H, Nayak L, Sinclair A, Henriquez NV, Sapey E, O’Mahony D, Lord JM (2001) Senescence in innate immune responses: reduced neutrophil phagocytic capacity and CD16 expression in elderly humans. J Leukoc Biol 70:881–886PubMedGoogle Scholar
  8. Cai W, Qing A, Guo P, Yan D, Hu F, Yang Q, Xu M, Fu Y, Zhou J, Tang X (2013) Clinical significance and functional studies of myeloid-derived suppressor cells in chronic hepatitis C patients. J Clin Immunol 33:798–808PubMedCrossRefGoogle Scholar
  9. Chan TC, Hung IF, Luk LK, Shea YF, Chan FH, Woo PC, Chu LW (2013) Functional status of older nursing home residents can affect the efficacy of influenza vaccination. J Gerontol A Biol 68:324–330CrossRefGoogle Scholar
  10. Cheng P, Corzo CA, Luetteke N, Yu B, Nagaraj S, Bui MM, Ortiz M, Nacken W, Sorg C, Vogl T, Roth J, Gabrilovich DI (2008) Inhibition of dendritic cell differentiation and accumulation of myeloid-derived suppressor cells in cancer is regulated by S100A9 protein. J Exp Med 205:2235–2249PubMedCentralPubMedCrossRefGoogle Scholar
  11. Chinn IK, Blackburn CC, Manley NR, Sempowski GD (2012) Changes in primary lymphoid organs with aging. Semin Immunol 24:309–320PubMedCentralPubMedCrossRefGoogle Scholar
  12. Diaz-Montero CM, Salem ML, Nishimura MI, Garrett-Mayer E, Cole DJ, Montero AJ (2009) Increased circulating myeloid-derived suppressor cells correlated with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol Immunother 58:49–59PubMedCentralPubMedCrossRefGoogle Scholar
  13. Dranoff G, Jaffee E, Lazenby A, Golumbek P, Levitsky H, Brose K, Jackson V, Hamada H, Pardoll D, Mulligan RC (1993) Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci U S A 90:3539–3543PubMedCentralPubMedCrossRefGoogle Scholar
  14. du Plessis N, Loebernberg L, Kriel M, von Groote-Bidlingmaier F, Ribechini E, Loxton AG, van Helden PD, Lutz MB, Walzl G (2013) Increased frequency of myeloid-derived suppressor cells during active tuberculosis and after recent mycobacterium tuberculosis infection suppresses T-cell function. Am J Respir Crit Care Med 188:724–732PubMedCrossRefGoogle Scholar
  15. Duggal NA, Upton J, Phillips AC, Sapey E, Lord JM (2013) An age-related numerical and functional deficit in CD19 + CD24hiCD38hi B cells is associated with an increase in systemic autoimmunity. Aging Cell 12:873–881PubMedCentralPubMedCrossRefGoogle Scholar
  16. Enioutina EY, Bareyan D, Daynes RA (2011) A role for immature myeloid cells in immune senescence. J Immunol 186:697–707PubMedCrossRefGoogle Scholar
  17. Feng PH, Lee KY, Chang YL, Chan YF, Kuo LW, Lin TY, Chung FT, Kuo CS, YU CT, Lin SM, Wang CH, Chow CL, Huang CD, Kuo HP (2013) CD14(+) S100A9(+) monocytic myeloid-derived suppressor cells and their clinical relevance in non-small cell lung cancer. Am J Respir Crit Care Med 186:1025–1036CrossRefGoogle Scholar
  18. Finke J, Ko J, Rini B, Rayman P, Ireland J, Cohen P (2011) MDSC as a mechanism of tumor escape from sunitinib mediated-anti-angiogenic therapy. Int Immunopharmacol 11:856–861PubMedCrossRefGoogle Scholar
  19. Flores-Borja F, Bosma A, Ng D, Reddy V, Ehrenstein MR, Isenberg DA, Mauri C (2013) CD19 + CD24hiCD38hi B cells maintain regulatory T cells while limiting TH1 and TH17 differentiation. Sci Transl Med 5:173CrossRefGoogle Scholar
  20. Franceschi C (2007) Inflammaging as a major characteristic of old people: can it be prevented or cured? Nutr Rev 65:S173–S176PubMedCrossRefGoogle Scholar
  21. Franceschi C, Bonafè M (2003) Centenarians as a model for healthy aging. Biochem Soc Trans 31:457PubMedCrossRefGoogle Scholar
  22. Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9:162–174PubMedCentralPubMedCrossRefGoogle Scholar
  23. Gabrilovich D, Ishida T, Oyama T, Ran S, Kravtsov V, Nadaf S, Carbone DP (1998) Vascular endothelial growth factor inhibits the development of dendritic cells and dramatically affects the differentiation of multiple hematopoietic lineages in vivo. Blood 92:4150–4166PubMedGoogle Scholar
  24. Grizzle WE, Xu X, Zhang S, Stockard CR, Liu C, Yu S, Wang J, Mountz JD, Zhang HG (2007) Age-related increase of tumor susceptibility is associated with myeloid-derived suppressor cell mediated suppression of T cell cytotoxicity in recombinant inbred BXD12 mice. Mech Ageing Dev 128:672–680PubMedCrossRefGoogle Scholar
  25. Guerra-Laso JM, González-Garcia S, González-Cortés C, Diez-Tascón C, López-Medrano R, Rivero-Lezcano OM (2013) Macrophages from elders are more permissive to intracellular multiplication of Mycobacterium tuberculosis. Age (Dordr) 35:1235–1250CrossRefGoogle Scholar
  26. Haile LA, von Wasielewski R, Gamrekelashvili J, Krüger C, Bachmann O, Westendorf AM, Buer J, Liblau R, Manns MP, Korangy F, Greten TF (2008) Myeloid-derived suppressor cells in inflammatory bowel disease: a new immunoregulatory pathway. Gastroenterology 135:871–881PubMedCrossRefGoogle Scholar
  27. Harari O, Liao JK (2004) Inhibition of MHC II gene transcription by nitric oxide and antioxidants. Curr Pharm Des 10:893–898PubMedCentralPubMedCrossRefGoogle Scholar
  28. Hazeldine J, Hampson P, Lord JM (2012) Reduced release and binding of perforin at the immunological synapse underlies the age-related decline in natural killer cell cytotoxicity. Aging Cell 11:751–759PubMedCrossRefGoogle Scholar
  29. Hearps AC, Martin GE, Angelovich TA, Cheng WJ, Maisa A, Landay AL, Jawaroski A, Crowe SM (2012) Aging is associated with chronic innate immune activation and dysregulation of monocyte phenotype and function. Aging Cell 11:867–875PubMedCrossRefGoogle Scholar
  30. Heim CE, Vidlak D, Ted S, Kozel JA, Holzapfel M, Muirhead DE, Kielian T (2014) Myeloid-derived suppressor cells contribute to Staphylococcus aureus orthopedic biofilm infection. J Immunol 192:3778–3792PubMedCrossRefGoogle Scholar
  31. Heithoff DM, Enioutina EY, Bareyan D, Daynes RA, Mahan MJ (2008) Conditions that diminish myeloid-derived suppressor cell activities stimulate cross-protective immunity. Infect Immun 76:5191–5199PubMedCentralPubMedCrossRefGoogle Scholar
  32. Hoechst B, Gamrekelashvili J, Manns MP, Greten TF, Korangy F (2011) Plasticity of human Th17 cells an iTregs is orchestrated by different subsets of myeloid cells. Blood 117:6532–6541PubMedCrossRefGoogle Scholar
  33. Hurez V, Daniel BJ, Sun L, Liu AJ, Ludwig SM, Kious MJ, Thibodeaux SR, Pandeswara S, Murthy K, Livi CB, Wall S, Brumlik MJ, Shin T, Zhang B, Curiel TJ (2012) Mitigating age-related immune dysfunction heightens the efficacy of tumor immunotherapy in aged mice. Cancer Res 72:2089–2099PubMedCentralPubMedCrossRefGoogle Scholar
  34. Hwang KA, Kim HR, Kang I (2009) Aging and human CD4+ regulatory T cells. Mech Ageing Dev 130:509–517PubMedCentralPubMedCrossRefGoogle Scholar
  35. Iannou M, Alissafi T, Lazaridis I, Deraos G, Matsoukas J, Gravanis A, Mastorodemos V, Plaitakis A, Sharpe A, Boumpas D, Verginins P (2012) Crucial role of granulocytic myeloid-derived suppressor cells in the regulation of central nervous system autoimmune disease. J Immunol 188:1136–1146CrossRefGoogle Scholar
  36. Iclozan C, Antonia S, Chiappori A, Chen DT, Gabrilovich D (2013) Therapeutic regulation of myeloid-derived suppressor cells and immune response to cancer vaccine in patients with extensive stage of small cell lung cancer. Cancer Immunol Immunother 62:909–918PubMedCentralPubMedCrossRefGoogle Scholar
  37. Irvine KM, Burns CJ, Wilks AF, Su S, Hume DA, Sweet MJ (2006) A CSF-1 receptor kinase inhibitor targets effector functions and inhibits pro-inflammatory cytokine production from murine macrophage populations. FASEB 20:1921–1923CrossRefGoogle Scholar
  38. Iwasa K, Yoshikawa H, Samuraki M, Shinohara M, Hamaguchi T, Ono K, Nakamura H, Yamada M (2014) Myasthenia gravis: predictive factors associated with the synchronized elevation of anti-acetylcholine receptor antibody titer in Kanazawa, Japan. J Neuroimmunol 267:97–101PubMedCrossRefGoogle Scholar
  39. Jackson ML, Nelson JC, Weiss NS, Neuzil KM, Barlow W, Jackson LA (2008) Influenza vaccination and risk of community-acquired pneumonia in immunocompetent elderly people: a population-based, nested case–control study. Lancet 372:398–405PubMedCrossRefGoogle Scholar
  40. Jagger A, Shomojima Y, Goronzy JJ, Weyand CM (2014) Regulatory T cells and the immune aging process: a mini review. Gerontology 60:130–137PubMedCrossRefGoogle Scholar
  41. Jiao Z, Hua S, Wang W, Wang H, Gao J, Wang X (2013) Increased circulating myeloid-derived suppressor cells correlated negatively with Th17 cells in patients with rheumatoid arthritis. Scand J Rheumatol 42:85–90PubMedCrossRefGoogle Scholar
  42. Jitschin R, Braun M, Büttner M, Dettmer-Wilde K, Bricks J, Berger J, Eckart MJ, Krause SW, Oefner PJ, Le Blanc K, Mackensen A, Mougiakakos D (2014) CLL-cells induce IDOhi CD14+HLA-DRlo myeloid-derived suppressor cells that inhibit T-cell responses and promote TRegs. Blood 124(5):750–760Google Scholar
  43. Jordan KR, Amaria RN, Ramirez O, Callihan EB, Gao D, Borakove M, Manthey E, Borges VF, McCarter MD (2013) Myeloid-derived suppressor cells are associated with disease progression and decreased overall survival in advanced-stage melanoma patients. Cancer Immunol Immunother 62:1711–1722Google Scholar
  44. Kalathil S, Lugade AA, Miller A, Iyer R, Thanavala Y (2013) Higher frequencies of GARP(+)CTLA-4(+)Foxp3(+) T regulatory cells and myeloid-derived suppressor cells in hepatocellular carcinoma patients are associated with impaired T-cell functionality. Cancer Res 73:2435–2444PubMedCentralPubMedCrossRefGoogle Scholar
  45. Kaufman HL, Kim DW, DeRaffele G, Mitcham J, Coffin RS, Kim-Schulze S (2010) Local and distant immunity induced by intralesional vaccination with an oncolytic herpes virus encoding GM-CSF in patients with stage IIIc and IV melanoma. Ann Surg Oncol 17:718–730PubMedCrossRefGoogle Scholar
  46. Knippenberg S, Peelen E, Smolders J, Thewissen M, Menheere P, Cohen Tervaert JW, Hupperts R, Damoiseaux J (2011) Reduction in IL-10 producing B cells (Breg) in multiple sclerosis is accompanied by a reduced naïve/memory Breg ratio during a relapse but not in remission. J Neuroimmunol 239:80–86PubMedCrossRefGoogle Scholar
  47. Ko JS, Zea AH, Rini BI, Ireland JL, Elson P, Cohen P, Golshayan A, Rayman PA, Wood L, Garcia J, Dreicer R, Bukowski R, Finke JH (2009) Sunitinib mediates reversal of myeloid-derived suppressor cell accumulation in renal cell carcinoma patients. Clin Cancer Res 15:2148–2157PubMedCrossRefGoogle Scholar
  48. Krause SW, Oefner PJ, Le Branc K, Mackensen A, Mougiakakos D (2014) CLL-cells induce IDOhi CD14+HLA-DRlow myeloid derived suppressor cells that inhibit T-cell responses and promote Tregs. Blood. doi: 10.1182/ blood-2013-12-546416 Google Scholar
  49. Kurkó J, Vida A, Glant TT, Scanzello CR, Katz RS, Nair A, Mikecz K, Szekancz Z (2014) Identification of myeloid-derived suppressor cells in the synovial fluid of patients with rheumatoid arthritis: a pilot study. BMC Musculoskelet Disord 15:281PubMedCentralPubMedCrossRefGoogle Scholar
  50. Kusmartsev S, Su Z, Heiser A, Dannuell J, Eruslanov E, Kübler H, Yancei D, Dahm P, Vieweg J (2008) Reversal of myeloid cell-mediated immunosuppression in patients with metastatic renal cell carcinoma. Clin Cancer Res 14:8270–8278PubMedCrossRefGoogle Scholar
  51. Lages Cs, Suffia I, Velilla PA, Huang B, Warshaw G, Hildeman DA, Belkaid Y, Chougnet C (2008) Functional regulatory T cells accumulate in aged hosts and promote chronic infectious disease reactivation. J Immunol 181:1835–1848Google Scholar
  52. Levin MJ (2012) Immune senescence and vaccines to prevent herpes zoster in older persons. Curr Opin Immunol 24:494–500PubMedCrossRefGoogle Scholar
  53. Li H, Han Y, Guo Q, Zhang M, Cao X (2009) J Immunol 182:240–249PubMedCrossRefGoogle Scholar
  54. Luycx A, Schouppe E, Rutgeerts O, Lenaerts C, Fevery S, Devos T, Dierickx M, Waer M, Van Ginderachter JA, Billiau AD (2012) G-CSF stem cell mobilization in human donors induces polymorphonuclear and mononuclear myeloid-derived suppressor cells. Clin Immunol 143:83–87CrossRefGoogle Scholar
  55. Ma C, Kapanadze T, Gamrekelashvili J, Manns MP, Korangy F, Greten TF (2012) Anti-Gr-1- antibody depletion fails to eliminate hepatic myeloid-derived suppressor cells in tumor-bearing mice. J Leukoc Biol 92:1199–1206PubMedCentralPubMedCrossRefGoogle Scholar
  56. Mandruzzato S, Solito S, Falisi E, Francescato S, Chiarion-Sileni V, Mocellin S, Zanon A, Rossi CR, Nitti D, Bront V, Zanovello P (2009) IL4Ralpha + myeloid-derived suppressor cells expansion in cancer patients. J Immunol 182:6562–6568PubMedCrossRefGoogle Scholar
  57. Mistry M, Parkin DM, Ahmad AS, Sasieni P (2011) Cancer incidence in the United Kingdom: projections to the year 2030. Br J Cancer 105:1795–1803PubMedCentralPubMedCrossRefGoogle Scholar
  58. Mitchell WA, Lang PO, Aspinall R (2010) Tracing thymic output in older individuals. Clin Exp Immunol 161:497–503PubMedCentralPubMedCrossRefGoogle Scholar
  59. Monto AS (2010) Seasonal influenza and vaccination coverage. Vaccine 28(S4):D33–D44PubMedCrossRefGoogle Scholar
  60. Morales JK, Kmieciak M, Graham L, Feldmesser M, Bear HD, Manjili MH (2009) Adoptive transfer of HER2/neu-specific T cells expanded with alternative gamma chain cytokines mediate tumor regression when combined with the depletion of myeloid-derived suppressor cells. Cancer Immunol Immunother 58:941–953PubMedCentralPubMedCrossRefGoogle Scholar
  61. Moro-Garcia MA, Alonso-Arias R, López-Larrea C (2013) When aging reaches CD4+ T-cells: phenotypic and functional changes. Front Immunol 4:107PubMedCentralPubMedCrossRefGoogle Scholar
  62. Nefedova Y, Fishman M, Sherman S, Wang X, Beg AA, Gabrilovich DI (2007) Mechanism of all-trans retinoic acid effect on tumor-associated myeloid-derived suppressor cells. Cancer Res 76:11021–11028CrossRefGoogle Scholar
  63. NICER: Foundation National Institute for Cancer Epidemiology and Registration (NICER) (2014) Accessed May 21, 2014
  64. Ochoa JB, Strange J, Kearney P, Gellin G, Endean E, Fitzpatrick E (2001) Effects of L-arginine o the proliferation of T lymphocyte subpopulations. JPEN J Parenter Enteral Nutr 25:23–29PubMedCrossRefGoogle Scholar
  65. Onyema OO, Njemini R, Bautmans I, Renmans W, De Waele M, Mets T (2012) Cellular aging and senescence characteristics of human T-lymphocytes. Biogerontology 13:169–181PubMedCrossRefGoogle Scholar
  66. Panda A, Arjona A, Sapey E, Bai F, Fikrig E, Montgomery RR, Lord JM, Shaw AC (2009) Human innate immunosenescence: causes and consequences for immunity in old age. Trends Immunol 30:325–333PubMedCentralPubMedCrossRefGoogle Scholar
  67. Pico de Coaña Y, Pschkel I, Gentilcore G, Mao Y, Nyström M, Hanssom J, Masucci G, Kiessling R (2013) Ipilimumab treatment results in an early decrease in the frequency of circulating granulocytic myeloid-derived suppressor cells as well as their Arginase1 production. Cancer Immunol Res 1:158–162PubMedCrossRefGoogle Scholar
  68. Pico de Coaña Y, Masucci G, Hansson J, Kiessling R (2014) Myeloid-derived suppressor cells and their role in CTLA-4 blockade therapy. Cancer Immunol Immunother 63:977–983PubMedCrossRefGoogle Scholar
  69. Pohla H, Burchner A, Stadlbauer B, Frankenberger B, Stevanovic S, Walter S, Frank R, Schwachula T, Olek S, Kopp J, Willimsky G, Stief CG, Hofstetter A, Pezzutto A, Blankenstein T, Oberneder R, Schendel DJ (2013) High immune response rates and decreased frequencies of regulatory T cells in metastatic renal cell carcinoma patients after tumor cell vaccination. Mol Med 18:1499–1508PubMedGoogle Scholar
  70. Poschke I, Mougiakakos D, Hansson J, Masucci GV, Kiessling R (2010) Immature immunosuppressive CD14 + HLA-DR-/low cells in melanoma patients are Stat3hi and overexpress CD80, CD83, and DC-sign. Cancer Res 70:4335–4345PubMedCrossRefGoogle Scholar
  71. Qin A, Cai W, Pan T, Wu K, Yang Q, Wang N, Liu Y, Yan D, Hu F, Guo P (2013) Expansion of monocytic myeloid-derived suppressor cells dampens T cell function in HIV-1-seropositive individuals. J Virol 87:1477–1490PubMedCentralPubMedCrossRefGoogle Scholar
  72. Rivoltini L, Carrabba M, Huber V, Castelli C, Novellino L, Dalerba P, Mortarini R, Arancia G, Anichini A, Fais S, Parmiani G (2002) Immunity to cancer: attack and escape in T lymphocyte-tumor cell interaction. Immunol Rev 188:97–113PubMedCrossRefGoogle Scholar
  73. Rodriguez PC, Quiceno DG, Ochoa AC (2007) L-arginine availability regulates T-lymphocyte cell-cycle progression. Blood 109:1568–1573PubMedCentralPubMedCrossRefGoogle Scholar
  74. Ryba-Stanislawowska M, Skrzypkowska M, Myslowska J, Mysliwiec M (2013) The serum IL-6 profile and Treg/Th17 peripheral cell populations in patients with type 1 diabetes. Mediator Inflamm. doi: 10.1155/2013/205284 Google Scholar
  75. Schilling B, Sucker A, Griewank K, Zhao F, Weide B, Görgens A, Giebel B, Schadendorf D, Paschen A (2013) Vemurafenib reverses immunosuppression by myeloid-derived suppressor cells. Int J Cancer 133:1653–1663PubMedCrossRefGoogle Scholar
  76. Schimtt V, Rink L, Uciechowski P (2013) The Th17/Treg imbalance is disturbed during aging. Exp Gerontol 48:1379–1386CrossRefGoogle Scholar
  77. Schmielau J, Finn OJ (2001) Activated granulocytes and granulocyte derived hydrogen peroxide are the underlying mechanism of suppression of T-cell function in advanced cancer patients. Cancer Res 61:4756–4760PubMedGoogle Scholar
  78. Serafini P, Carbley R, Noonan KA, Tan G, Bronte V, Borrello I (2004) High-dose granulocyte-macrophage colony-stimulating factor-producing vaccines impair the immune response through the recruitment of myeloid suppressor cells. Cancer Res 64:6337–6343PubMedCrossRefGoogle Scholar
  79. Su DM, Aw D, Palmer DB (2013) Immunosenescence: a product of the environment? Curr Opin Immunol 25:498–503PubMedCrossRefGoogle Scholar
  80. Sunderkötter C, Nikolic T, Dillon MJ, Van Rooijen N, Stehling M, Drevets DA, Leenen PJ (2004) Subpopulations of mouse blood monocytes differ in maturation stage and inflammatory response. J Immunol 172:4410–4417PubMedCrossRefGoogle Scholar
  81. Tam JW, Kullas AL, Mena P, Bliska JB, van der Velden AW (2014) CD11b+Ly6Chi Ly6G immature myeloid cells recruited in response to Salmonella enterica Serovar Typhimurium infection exhibit protective and immunosuppressive properties. Infect Immun 82:2606–2614PubMedCentralPubMedCrossRefGoogle Scholar
  82. Tarhini AA, Edington H, Butterfield LH, Lin Y, Shuai Y, Tawbi H, Sander C, Yin Y, Holtzman M, Johnson J, Rao UN, Kirkwood JM (2014) Immune monitoring of the circulation and the tumor microenvironment in patients with regionally advanced melanoma receiving neoadjuvant ipilimumab. PLoS One 9(2):e87705PubMedCentralPubMedCrossRefGoogle Scholar
  83. Thaci B, Ahmed AU, Ulasov IV, Wainwright DA, Nigam P, Auffinger B, Tobias AL, Han Y, Zhang L, Moon KS, Lesniak MS (2014) Depletion of myeloid-derived suppressor cells during interleukin-12 immunogene therapy does not confer a survival advantage in experimental malignant glioma. Cancer Gene Ther 21:38–44PubMedCentralPubMedCrossRefGoogle Scholar
  84. Trager N, Smith A, Wallace Iv G, Azuma M, Inoue J, Beeson C, Haque A, Banik NL (2014) Effects of a novel orally administered calpain inhibitor SNJ-1945 on immunomodulation and neurodegeneration in a murine model of multiple sclerosis. J Neurochem. doi: 10.1111/jnc.12659 PubMedGoogle Scholar
  85. Tsiganov EM, Verbina EM, Radaeva TV, Sosunov VV, Kosmiadi GA, Nikitina IY, Lyadova IV (2014) Gr-1dimCD11b + immature myeloid-derived suppressor cells but not neutrophils are markers of lethal tuberculosis infection in mice. J Immun 192:4718–4727PubMedCrossRefGoogle Scholar
  86. Ugel S, Delpozzo F, Desantis G, Papalini F, Simonato F, Sonda N, Ziolio S, Bronte V (2009) Therapeutic targeting of myeloid-derived suppressor cells. Curr Opin Pharmacol 9:470–481PubMedCrossRefGoogle Scholar
  87. Valencia X, Yarboro C, Illei G, Lipsky PE (2007) Deficient CD4 + CD25high T regulatory cell function in patients with active systemic lupus erythematosus. J Immunol 178:2579–2588PubMedCrossRefGoogle Scholar
  88. Verschoor CP, Johnstone J, Millar J, Dorrington MG, Habibagahi M, Lelic A, Loeb M, Bramson JL, Bowdish DME (2013) Blood CD33(+)HLA-DR(−) myeloid-derived suppressor cells are increased with age and a history of cancer. J Leukoc Biol 93:633–637PubMedCentralPubMedCrossRefGoogle Scholar
  89. Vollbrecht T, Stirner R, Tufman A, Roider J, Huber RM, Bogner JR, Lechner A, Bourquin C, Draenert R (2012) Chronic progressive HIV-1 infection is associated with elevated levels of myeloid-derived suppressor cells. AIDS 26:F31–F37PubMedCrossRefGoogle Scholar
  90. Vuk-Pavlović BPA, Lin Y, Qin R, Szumlanski CL, Zhao X, Dietz AB (2010) Immunosuppressive CD14 + HLA-DRlow/- monocytes in prostate cancer. Prostate 70:443–455PubMedCentralPubMedGoogle Scholar
  91. Wenish C, Patruta S, Daxböck F, Krause R, Hörl W (2000) Effect of age on human neutrophil function. J Leukoc Biol 67:40–45Google Scholar
  92. World Health Organization (2005) Influenza vaccines. Wkly Epidemiol Rec 80(33):279–287Google Scholar
  93. World Health Organization (WHO) (2011). Influenza (Seasonal). Fact sheet N°211. April 2009. [updated 2011]. Available from: Accessed November 30, 2011
  94. Yang B, Wang X, Jiang J, Zhai F, Cheng X (2014) Identification of 244-expressing myeloid-derived suppressor cells in patients with active tuberculosis. Immunol Lett 158:66–72PubMedCrossRefGoogle Scholar
  95. Yao X, Hamilton RG, Weng NP, Xue QL, Bream JH, Li H, Tian J, Yeh SH, Resnick B, Xu X, Walston J, Fried LP, Leng SX (2011) Frailty is associated with impairment of vaccine-induced antibody response and increase in post-vaccination influenza infection in community-dwelling older adults. Vaccine 29:5015–5021PubMedCentralPubMedCrossRefGoogle Scholar
  96. Youn JI, Nagaraj S, Collazo M, Gabrilovich DI (2008) Subsets of myeloid-derived suppressor cells in tumor-bearing mice. J Immunol 181:5791–5802PubMedCentralPubMedCrossRefGoogle Scholar
  97. Yu J, Du W, Yan F, Wang Y, Li H, Cao S, Yu W, Shen C, Liu J, Ren X (2013) Myeloid-derived suppressor cells suppress antitumor immune responses through IDO expression and correlate with lymph node metastasis in patients with breast cancer. J Immunol 190:3783–3797PubMedCrossRefGoogle Scholar
  98. Zea AH, Rodriguez PC, Atkins MB, Hernandez C, Signoretti S, Zabaleta J, McDermott D, Quiceno D, Youmans A, O’Neill A, Mier J, Ochoa AC (2005) Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: A mechanism of tumor evasion. Cancer Res 65:3044–3048PubMedGoogle Scholar
  99. Zeng QL, Yang B, Sun HQ, Feng GH, Jin L, Zou ZS, Zhang Z, Zhang JY, Wang FS (2014) Myeloid-derived suppressor cells are associated with viral persistence and down regulation of TCR ζ chain expression on CD8+ T cells in chronic hepatitis C patients. Mol Cells 37:66–73PubMedCentralPubMedCrossRefGoogle Scholar
  100. Zhu B, Bando Y, Xiao S, Yang K, Anderson AC, Kichroo VK, Khoury SJ (2007) CD11b + Ly-6Chi suppressive monocytes in experimental autoimmune encephalomyelitis. J Immunol 179:5228–5237PubMedCrossRefGoogle Scholar

Copyright information

© American Aging Association 2014

Authors and Affiliations

  • Valquiria Bueno
    • 1
    Email author
  • Osvaldo Augusto Sant’Anna
    • 2
  • Janet M Lord
    • 3
  1. 1.Department of Microbiology Immunology and ParasitologyUNIFESP Federal University of São PauloSão PauloBrazil
  2. 2.Laboratory of Immunochemistry—Butantan InstituteSão PauloBrazil
  3. 3.MRC-ARUK Centre for Musculoskeletal Ageing Research, School of Immunity and InfectionUniversity of BirminghamBirminghamUK

Personalised recommendations