Abstract
Myeloid-derived suppressor cells (MDSC) act regulating/suppressing immune responses and there are few evidences that these cells increase in healthy old individuals. MDSCs impair the functions of T cells, NK cells, and dendritic cells through several pathways that include expression of arginase I, inducible nitric oxide synthase, release of reactive oxygen species and peroxynitrite. The role played by MDSCs in immune modulation may be beneficial or detrimental to the health of aging individuals depending on their development, phenotype, functions, and the pathological conditions. MDSCs have been extensively studied in cancer and more recently these cells were correlated with other pathological conditions such as sepsis, tuberculosis, COVID-19, autoimmune diseases, obesity, diabetes and neurodegenerative diseases. In patients with COVID-19 it has been reported that the increase of MDSC correlated with disease severity and fatal cases. Considering that COVID-19 has caused morbidity and mortality with a higher incidence in ageing individuals and especially in those with chronic diseases, the projection of how the frequency and suppressive function of MDSC could be increased in ageing can lead to the development of more appropriate therapies for the aged population.
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Abbreviations
- AD :
-
Alzheimer’s disease
- ANA :
-
Antinuclear antibody
- ARG-1 :
-
Arginase-1
- ASC :
-
Antibody secreting B-cells
- COVID-19 :
-
Corona virus disease
- CRPC :
-
Castration-resistant prostate cancer
- CSPC :
-
Castration-sensitive prostate cancer
- CTLA-4 :
-
Cytotoxic T-lymphocyte-associated protein 4
- G-MDSC :
-
Granulocytic Myeloid-derived suppressor cells
- GVAX :
-
Tumor vaccines composed of autologous tumor cells genetically modified to secrete granulocyte–macrophage colony-stimulating factor
- HBC :
-
Hepatitis C virus
- HBV :
-
Hepatitis B virus
- HDL-c :
-
High-density lipoprotein cholesterol
- IDO :
-
Indolamine-2,3-dioxygenase
- IFN-γ :
-
Interferon-gama
- IL-10 :
-
Interleukin-10
- iNOS :
-
Inducible nitric oxide synthase
- LOX1 :
-
Lectin-type oxidized low-density lipoprotein receptor-1
- MDSC :
-
Myeloid-derived suppressor cells
- MUC1 :
-
Mucine-1
- MS :
-
Multiple sclerosis
- NO :
-
Nitric oxide
- PD1 :
-
Programmed cell death protein 1
- PD-L1 :
-
Programmed cell death protein ligand 1
- PD-L2 :
-
Programmed cell death protein ligand 2
- PMN-MDSC :
-
Polymorphonuclear Myeloid-derived suppressor cells
- PPLNs :
-
Positive pelvic lymph nodes
- PSA :
-
Prostate-specific antigen
- RA :
-
Rheumatoid arthritis
- SARS-Cov-2 :
-
Severe acute respiratory syndrome coronavirus 2
- STAT3 :
-
Signal transducer and activator of transcription 3
- TB :
-
Mycobacterium tuberculosis
- TCR :
-
T-cell receptor
- TGF-β :
-
Transforming growth factor-beta
- TME :
-
Tumor microenvironment
- T1D :
-
Type 1 diabetes
- T2D :
-
Type 2 diabetes
References
Agrati C (2020) Expansion of myeloid-derived suppressor cells in patients with severe coronavirus disease (COVID-19). Cell Death Differ 27:3196–3207. https://doi.org/10.1038/s41418-020-0572-6
Alves AS, Ishimura ME, Duarte YAO, Bueno V (2018) Parameters of the immune system and vitamin d levels in old individuals. Front Immunol 9:1122. https://doi.org/10.3389/fimmu.2018.01122
Bao Y, Mo J, Ruan L, Li G (2015) Increased monocytic CD14+HLADRlow/- myeloid-derived suppressor cells in obesity. Mol Med Rep 11(3):2322–2328. https://doi.org/10.3892/mmr.2014.2927
Bertelli G, Trovato R, Ugel S et al (2019) Characterization of myeloid-derived suppressor cells in a patient with lung adenocarcinoma undergoing Durvalumab treatment: a case report. Clin Lung Cancer 20(4):e514–e516. https://doi.org/10.1016/j.cllc.2019.04.013
Bonomi M, Ahmed T, Addo S et al (2019) Circulating immune biomarkers as predictors of the response to pembrolizumab and weekly low dose carboplatin and paclitaxel in NSCLC and poor PS: An interim analysis. Oncol Lett 17(1):1349–1356. https://doi.org/10.3892/ol.2018.9724
Bueno V, Sant’Anna OA, Lord JM (2014) Ageing and myeloid-derived suppressor cells: possible involvement in immunosenescence and age-related disease. Age (Dordr) 36(6):9729. https://doi.org/10.1007/s11357-014-9729-x.
Calcinotto A, Spataro C, Zagato E et al (2018) IL-23 secreted by myeloid cells drives castration-resistant prostate cancer. Nature 559(7714):363–369. https://doi.org/10.1038/s41586-018-0266-0
Chai E, Zhang L, Li C (2019) LOX-1+ PMN-MDSC enhances immune suppression which promotes glioblastoma multiforme progression. Cancer Manag Res 11:7307–7315. https://doi.org/10.2147/CMAR.S210545
Chen S, Akbar SM, Miyake T et al (2015) Diminished immune response to vaccinations in obesity: role of myeloid-derived suppressor and other myeloid cells. Obes Res Clin Pract 9(1):35–44. https://doi.org/10.1016/j.orcp.2013.12.006
Chen S et al (2017) Increased abundance of myeloid-derived suppressor cells and Th17 cells in peripheral blood of newly-diagnosed Parkinson’s disease patients. Neurosci Lett 648:21–25. https://doi.org/10.1016/j.neulet.2017.03.045
Choi J, Maeng HG, Lee SJ et al (2018) Diagnostic value of peripheral blood immune profiling in colorectal cancer. Ann Surg Treat Res 94(6):312–321. https://doi.org/10.4174/astr.2018.94.6.312
Condamine T, Dominguez GA, Youn JI, et al (2016) Lectin-type oxidized LDL receptor-1 distinguishes population of human polymorphonuclear myeloid-derived suppressor cells in cancer patients. Sci Immunol 1: aaf8943. https://doi.org/10.1126/sciimmunol.aaf8943
El Daker S, Sacchi A, Tempestilli M, et al (2015) Granulocytic myeloid derived suppressor cells expansion during active pulmonary tuberculosis is associated with high nitric oxide plasma level. PLoS One 10(4):e0123772. https://doi.org/10.1371/journal.pone.0123772
Diaz-Montero CM, Salem ML, Nishimura MI et al (2009) Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastatic tumor burden, and doxorubicin-cyclosphosphamide chemotherapy. Cancer Immunol Immunother 58(1):49–59. https://doi.org/10.1007/s.00262-008-0523-4
du Plessis N, Loebenberg L, Kriel M et al (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(6):724–732. https://doi.org/10.1164/rccm.201302-0249OC
Dubinski D, Wölfer J, Hasselblatt M et al (2016) CD4+ T effector memory cell dysfunction is associated with the accumulation of granulocytic myeloid- derived suppressor cells in glioblastoma patients. Neuro Oncol 18(6):807–818. https://doi.org/10.1093/neuonc/nov280
Falck-Jones S (2020) Functional myeloid-derived suppressor cells expand in blood but not airways of COVID-19 patients and predict disease severity. medRxiv, 2020.2009.2008.20190272. https://doi.org/10.1101/2020.09.08.20190 272
Fang Z, Li J, Yu X et al (2015) Polarization of monocytic myeloid-derived suppressor cells by Hepatitis B surface antigen is mediated via ERK/IL-6/STAT3 signaling feedback and restrains the activation of T cells in Chronic Hepatitis B virus infection. J Immunol 195(10):4873–4883. https://doi.org/10.4049/jimmunol.1501362
Fernández-Ruiz JC, Galindo De Ávila JC et al (2019) Myeloid-derived suppressor cells show different frequencies in diabetics and subjects with arterial hypertension. J Diabetes Res 2019:1568457. 10.1155/ 2019/1568457
Friedrich K, Sommer M, Strobel S et al (2019) Perturbation of the monocyte compartment in human obesity. Front Immunol 10:1874. https://doi.org/10.3389/fimmu.2019.01874
Gabrilovich DI, Nagaraj S (2009) Myeloid-derived-suppressor cells as regulators of the immune system. Nat Rev Immunol 9(3):162–174. https://doi.org/10.1038/nri2506
Goronzy JJ, Weyand CM (2012) Immune aging and autoimmunity. Cell Mol Life Sci 9(10):1615–1623. https://doi.org/10.1007/s00018-012-0970-0
Guo C, Hu F, Yi H et al (2016) Myeloid-derived suppressor cells have a proinflammatory role in the pathogenesis of autoimmune arthritis. Ann Rheum Dis 75(1):278–285. https://doi.org/10.1136/annrheumdis-2014-205508
Hassan M, Raslan HM, Eldin HG et al (2018) CD33+HLA-DR- myeloid-derived suppressor cells are increased in frequency in the peripheral blood of type1 diabetes patients with predominance of CD14+ subset. Open Access Maced J Med Sci 6(2):303–309. https://doi.org/10.3889/oamjms.2018.080
Hurme M, Korkki S, Lehtimäki T et al (2007) Autoimmunity and longevity: presence of antinuclear antibodies is not associated with the rate of inflammation or mortality in nonagerians. Mech Ageing Dev 128(5–6):407–408. https://doi.org/10.1016/j.mad.2007.03.001
Iannou M, Alissafi T, Lazaridis I, et al (2012) Crucial role of granulocytic myeloid-derived suppressor cells in the regulation of central nervous system autoimmune disease. J Immunol 188(3):1136–1146. https://doi.org/10.4049/jimmunol.1101816
Idorn M, Køllgaard T, Kongsted P et al (2014) Correlation between frequencies of blood monocytic myeloid-derived suppressor cells, regulatory T cells and negative prognostic markers in patients with castration-resistant metastatic prostate cancer. Cancer Immunol Immunother 63(11):1177–1187. https://doi.org/10.1007/s00262-014-1591-2
Janols H, Bergenfelz C, Allaoui R et al (2014) A high frequency of MDSCs in sepsis patients with the granulocytic subtype dominating in gram-positive cases. J Leukoc Biol 96(5):685–693. https://doi.org/10.1189/jlb.5HI0214-074R
Kimura T, McKolanis JR, Dzubinski LA et al (2013) MUC1 vaccine for individuals with advanced adenoma of the colon: a cancer immunoprevention feasibility study. Cancer Prev Res (Phila) 6(1):18–26. https://doi.org/10.1158/1940-6207.CAPR-12-0275
Knier B, Hiltensperger M, Sie C et al (2018) Myeloid-derived suppressor cells control B cell accumulation in the central nervous system during autoimmunity. Nat Immunol 19(12):1341–1351. https://doi.org/10.1038/s41590-018-0237-5
Kongsted P, Borch TH, Ellebaek E et al (2017) Dendritic cell vaccination in combination with docetaxel for patients with metastatic castration- resistant prostate cancer: A randomized phase II study. Cytotherapy 19(4):500–513. https://doi.org/10.1016/j.jcyt.2017.01.007
Kurkó J, Vida A, Glant TT et al (2014) Identification of myeloid-derived suppressor cells in the synovial fluid of patients with rheumatoid arthritis: a pilot study. BMC Musculoskelet Disord 15:281. https://doi.org/10.1186/1471-2474-15-281
Lang S, Bruderek K, Kaspar C et al (2018) Clinical relevance and suppressive capacity of human myeloid-derived suppressor cells subsets. Clin Cancer Res 24(19):4834–4844. https://doi.org/10.1158/1078-0432.CCR-17-3726
Lv Y, Cui M, Lv Z et al (2018) Expression and significance of peripheral myeloid-derived suppressor cells in chronic hepatitis B patients. Clin Res Hepatol Gastroenterol 42(5):462–469. https://doi.org/10.1016/j.clinre.2018.04.002
Mao Y, Poschke I, Wennerberg E et al (2013) Melanoma-educated CD14+ cells acquire a myeloid-derived suppressor cell phenotype through COX-2- dependent mechanisms. Cancer Res 73(13):3877–3887. https://doi.org/10.1158/0008-5472.CAN-12-4115
Marvel D, Gabrilovich DI (2015) Myeloid-derived suppressor cells in the tumor microenvironment: expect the unexpected. J Clin Invest 125(9):3356–3364. https://doi.org/10.1172/JCI80005
Mathias B, Delmas AL, Ozrazgat-Baslanti T et al (2017) The Sepsis, Critical Illness Research Center Investigators. Myeloid-derived suppressor cells are associated with chronic immune suppression after severe sepsis/septic shock. Ann Surg 265(4):827–834. https://doi.org/10.1097/SLA.00000000 00001783.
Navarro-Martín A, Galiana IL, Berenguer Frances MA et al (2018) Preliminary study of the effect of stereotactic body radiotherapy (SBRT) on the immune system in lung cancer patients unfit for surgery: immunophenotyping analysis. Int J Mol Sci 19(12): pii: E3963. https://doi.org/10.3390/ijms19123963.
Ostrand-Rosenberg S (2010) Myeloid-derived suppressor cells: more mechanisms for inhibiting antitumor immunity. Cancer Immunol Immunother 59:1593–1600. 10.1007/ s00262-010-0855-8
Pawelec G, Picard E, Bueno V et al (2021) MDSCs, ageing and inflammageing. Cell Immunol 362:104297. https://doi.org/10.1016/j.cellimm.2021.104297
Romano A, Parrinello NL, La Cava P et al (2018) PMN-MDSC and arginase are increased in myeloma and may contribute to resistance to therapy. Expert Rev Mol Diagn 18(7):675–683. https://doi.org/10.1080/14737159.2018.1470929
Salem ML, Zidan AA, Attia M et al (2017) IFN-α-based treatment of patients with chronic HCV show increased levels of cells with myeloid-derived suppressor cell phenotype and of IDO and NOS. Immunopharmacol Immunotoxicol 39(4):188–198. https://doi.org/10.1080/08923973.2017.1320670
Santegoests SJ, Stam AG, Lougheed SM et al (2014) Myeloid derived suppressor and dendritic cell subsets are related to clinical outcome in prostate cancer patients treated with prostate GVAX and Ipilimumab. J Immunother Cancer 2:31. https://doi.org/10.1186/s40425-019-0663-4
Schrijver IT, Théroude C, Roger T (2019) Myeloid-derived suppressor cells in sepsis. Front Immunol 10:327. https://doi.org/10.3389/fimmu.2019.00327
Sharma V, Dong H, Kwon E, Karnes RJ (2018) Positive pelvic lymph nodes in prostate cancer harbor immune suppressor cells to impair tumor-reactive T cells. Eur Urol Focus 4(1):75–79. https://doi.org/10.1016/j.euf.2016.09.003
Thome AD et al (2018) Functional alterations of myeloid cells during the course of Alzheimer’s disease. Mol Neurodegener 13:61. https://doi.org/10.1186/s13024-018-0293-1
Toor SM, Syed Khaja AS, El Salhat H et al (2016) Increased levels of circulating and tumor-infiltrating granulocytic myeloid cells in colorectal cancer patients. Front Immunol 7:560. https://doi.org/10.3389/fimmu.2016. 00560
Uhel F, Azzaoui I, Grégoire M et al (2017) Early expansion of circulating granulocytic myeloid-derived suppressor cells predicts development of nosocomial infections in patients with sepsis. Am J Respir Crit Care Med 196(3):315–327. https://doi.org/10.1164/rccm.201606-1143OC
Veglia F, Perego M, Gabrilovich D (2018) Myeloid-derived suppressor cells coming of age. Nat Immunol 19(2):108–119. https://doi.org/10.1038/s41590-017-0022-x
Verschoor CP, Johnstone J, Millar J et al (2013) Blood CD33(+)HLA-DR(-) myeloid-derived suppressor cells are increased with age and a history of cancer. J Leukoc Biol 93(4):633–637. https://doi.org/10.1189/jlb.0912461
Wesolowski R, Duggan MC, Stiff A et al (2017) Circulating myeloid-derived suppressor cells increase in patients undergoing neo-adjuvant chemotherapy for breast cancer. Cancer Immunol Immunother 66:1437–1447. https://doi.org/10.1007/s00262-017-2038-3
Whitfield-Larry F, Felton J, Buse J, Su MA (2014) Myeloid-derived suppressor cells are increased in frequency but not maximally suppressive in peripheral blood of Type 1 Diabetes Mellitus patients. Clin Immunol 153(1):156–164. https://doi.org/10.1016/j.clim.2014.04.006
Wu H, Zhen Y, Ma Z, et al (2016) Arginase-1-dependent promotion of TH17 differentiation and disease progression by MDSCs in systemic lupus erythematosus. Sci Transl Med 8(331):331ra40. 10.1126/ scItranslmed.aae0482.
Yu J, Du W, Yan F et al (2013) Myeloid-derived suppressor cells suppress antitumor immune response through IDO expression and correlate with lymph node metastasis in patients with breast cancer. J Immunol 190(7):3783–3797. https://doi.org/10.4049/jimmunol.1201449
Zeng QL, Yang B, Sun HQ et al (2014) Myeloid-derived suppressor cells are associated with viral persistence and down regulation of TCRζ chain expression on CD8(+) T cells in chronic hepatitis C patients. Mol Cells 37(1):66–73. https://doi.org/10.14348/molcells.2014.2282
Zhu J, Chen S, Wu L et al (2018) The expansion of myeloid-derived suppressor cells is associated with joint inflammation in rheumatic patients with arthritis. Biomed Res Int 2018:5474828. https://doi.org/10.1155/2018/5474828
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Valquiria Bueno is funded by the CAPES PrInt UNIFESP no 88881.310735/2018-01
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Bueno, V., Pawelec, G. (2022). Myeloid-Derived Suppressive Cells in Ageing and Age-Related Diseases. In: Bueno, V., Pawelec, G. (eds) Healthy Longevity and Immune System. Healthy Ageing and Longevity, vol 16. Springer, Cham. https://doi.org/10.1007/978-3-030-87532-9_4
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