Клиническое значение экспрессии гена PRAME при онкогематологических заболеваниях

В.А. Мисюрин

ФГБУ «НМИЦ онкологии им. Н.Н. Блохина» Минздрава России, Москва, Каширское ш., д. 24, 115478

Для переписки: Всеволод Андреевич Мисюрин, канд. биол. наук, Каширское ш., д. 24, Moсква, Российская Федерация, 115478; тел. +7(985)436-30-19; e-mail: vsevolod.misyurin@gmail.com

Для цитирования: Мисюрин В.А. Клиническое значение экспрессии гена PRAME при онкогематологических заболеваниях. Клиническая онкогематология. 2018;11(1):26–33.

DOI: 10.21320/2500-2139-2018-11-1-26-33


РЕФЕРАТ

Хотя и активность PRAME была впервые установлена при солидных опухолях, данный ген чрезвычайно часто экспрессируется при онкогематологических заболеваниях. Ген PRAME может быть использован как надежный биомаркер наличия опухолевых клеток. Определение транскриптов PRAME используется при мониторинге минимальной остаточной болезни и диагностике молекулярного рецидива. При проведении экспериментов с PRAME-экспрессирующими линиями лейкозных клеток получены противоречивые результаты. По этой причине объяснить наблюдаемое влияние экспрессии PRAME на прогноз очень сложно. Тем не менее при хронических миелопролиферативных заболеваниях и хроническом миелоидном лейкозе активность PRAME связана с худшим прогнозом, а при острых лейкозах лимфоидной и миелоидной направленности — с лучшим. Несмотря на большой объем клинических наблюдений, при некоторых нозологических формах влияние экспрессии PRAME на прогноз остается неизвестным. В настоящем обзоре литературы широко представлены известные данные об экспрессии гена PRAME при онкогематологических заболеваниях.

Ключевые слова: PRAME, лейкозы, лимфомы, прогноз.

Получено: 14 сентября 2017 г.

Принято в печать: 2 декабря 2017 г.

Читать статью в PDF 

ЛИТЕРАТУРА

  1. Ikeda H, Lethe B, Lehmann F, et al. Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor. Immunity. 1997;6(2):199–208. doi: 10.1016/S1074-7613(00)80426-4.
  2. Greiner J, Ringhoffer M, Simikopinko O, et al. Simultaneous expression of different immunogenic antigens in acute myeloid leukemia. Exp Hematol. 2000;28(12):1413–22. doi: 10.1016/S0301-472X(00)00550-6.
  3. Epping MT, Wang L, Edel MJ, et al. The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling. Cell. 2005;122(6):835–47. doi: 10.1016/j.cell.2005.07.003.
  4. De Carvalho DD, Mello BP, Pereira WO, Amarante-Mendes GP. PRAME/EZH2-mediated regulation of TRAIL: a new target for cancer therapy. Curr Mol Med. 2013;13(2):296–304. doi: 10.2174/156652413804810727.
  5. Costessi A, Mahrour N, Tijchon E, et al. The tumour antigen PRAME is a subunit of a Cul2 ubiquitin ligase and associates with active NFY promoters. EMBO J. 2011;30(18):3786–98. doi: 10.1038/emboj.2011.262.
  6. Kim HL, Seo YR. Molecular and genomic approach for understanding the gene-environment interaction between Nrf2 deficiency and carcinogenic nickel-induced DNA damage. Oncol Rep. 2012;28(6):1959–67. doi: 10.3892/or.2012.2057.
  7. Yao J, Caballero OL, Yung WK, et al. Tumor subtype-specific cancer-testis antigens as potential biomarkers and immunotherapeutic targets for cancers. Cancer Immunol Res. 2014;2(4):371–9. doi: 10.1158/2326-6066.CIR-13-0088.
  8. van Baren N, Chambost H, Ferrant A, et al. PRAME, a gene encoding an antigen recognized on a human melanoma by cytolytic T cells, is expressed in acute leukaemia cells. Br J Haematol. 1998;102(5):1376–9. doi: 10.1046/j.1365-2141.1998.00982.x.
  9. Oehler VG, Guthrie KA, Cummings CL, et al. The preferentially expressed antigen in melanoma (PRAME) inhibits myeloid differentiation in normal hematopoietic and leukemic progenitor cells. Blood. 2009;114(15):3299–308. doi: 10.1182/blood-2008-07-170282.
  10. Roman-Gomez J, Jimenez-Velasco A, Agirre X, et al. Epigenetic regulation of PRAME gene in chronic myeloid leukemia. Leuk Res. 2007;31(11):1521–8. doi: 10.1016/j.leukres.2007.02.016.
  11. Ortmann CA, Eisele L, Nuckel H, et al. Aberrant hypomethylation of the cancer–testis antigen PRAME correlates with PRAME expression in acute myeloid leukemia. Ann Hematol. 2008;87(10):809–18. doi: 10.1007/s00277-008-0514-8.
  12. Gutierrez-Cosio S, de la Rica L, Ballestar E, et al. Epigenetic regulation of PRAME in acute myeloid leukemia is different compared to CD34+ cells from healthy donors: Effect of 5-AZA treatment. Leuk Res. 2012;36(7):895–9. doi: 10.1016/j.leukres.2012.02.030.
  13. Arons E, Suntum T, Margulies I, et al. PRAME expression in Hairy Cell Leukemia. Leuk Res. 2008;32(9):1400–6. doi: 10.1016/j.leukres.2007.12.010.
  14. Steinbach D, Schramm A, Eggert A, et al. Identification of a Set of Seven Genes for the Monitoring of Minimal Residual Disease in Pediatric Acute Myeloid Leukemia. Clin Cancer Res. 2006;12(8):2434–41. doi: 10.1158/1078-0432.CCR-05-2552.
  15. Matsushita M, Ikeda H, Kizaki M, et al. Quantitative monitoring of the PRAME gene for the detection of minimal residual disease in leukaemia. Br J Haematol. 2001;112(4):916–26. doi: 10.1046/j.1365-2141.2001.02670.x.
  16. Tajeddine N, Millard I, Gailly P, Gala JL. Real-time RT-PCR quantification of PRAME gene expression for monitoring minimal residual disease in acute myeloblastic leukaemia. Clin Chem Lab Med. 2006;44(5):548–55. doi: 10.1515/CCLM.2006.106.
  17. Schneider V, Zhang L, Rojewski M, et al. Leukemic progenitor cells are susceptible to targeting by stimulated cytotoxic T cells against immunogenic leukemia-associated antigens. Int J Cancer. 2015;137(9):2083–92. doi: 10.1002/ijc.29583.
  18. Гапонова Т.В., Менделеева Л.П., Мисюрин А.В. и др. Экспрессия опухолеассоциированных генов PRAME, WT1 и XIAP у больных множественной миеломой. Онкогематология. 2009;2:52–7. [Gaponova TV, Mendeleeva LP, Misyurin AV, et al. Expression of PRAME, WT1 and XIAP tumor-associated genes in patients with multiple myeloma. Onkogematologiya. 2009;2:52–7. (In Russ)]
  19. Абраменко И.В., Белоус Н.И., Крячок И.А. и др. Экспрессия гена PRAME при множественной миеломе. Терапевтический архив. 2004;74(7):77–81. [Abramenko IV, Belous NI, Kryachok IA, et al. Expression of PRAME gene in multiple myeloma. Terapevticheskii arkhiv. 2004;74(7):77–81. (In Russ)]
  20. Мисюрин В.А., Мисюрин А.В., Кесаева Л.А. и др. Новые маркеры прогрессирования хронического миелолейкоза. Клиническая онкогематология. 2014;7(2):206–12. [Misyurin VA, Misyurin AV, Kesayeva LA, et al. New molecular markers of CML progression. Klinicheskaya onkogematologiya. 2014;7(2):206–12. (In Russ)]
  21. van Baren N, Brasseur F, Godelaine D, et al. Genes encoding tumor-specific antigens are expressed in human myeloma cells. Blood. 1999;94(4):1156–64.
  22. Pellat-Deceunynck C, Mellerin M., Labarriere N, et al. The cancer germ-line genes MAGE-1, MAGE-3 and PRAME are commonly expressed by human myeloma cells. Eur J Immunol. 2000;30(3):803–9. doi: 10.1002/1521-4141(200003)30:3<803:AID-IMMU803>3.0.CO;2-P.
  23. Andrade VC, Vettore AL, Felix RS, et al. Prognostic impact of cancer/testis antigen expression in advanced stage multiple myeloma patients. Cancer Immun. 2008;8:2.
  24. Qin Y, Lu J, Bao L, et al. Bortezomib improves progression-free survival in multiple myeloma patients overexpressing preferentially expressed antigen of melanoma. Chin Med J (Engl). 2014;127(9):1666–71. doi: 10.3760/cma.j.issn.0366-6999.20132356.
  25. Proto-Siqueira R, Falcao RP, de Souza CA, et al. The expression of PRAME in chronic lymphoproliferative disorders. Leuk Res. 2003;27(5):393–6. doi: 10.1016/S0145-2126(02)00217-5.
  26. Proto-Siqueira R, Figueiredo-Pontes LL, Panepucci RA, et al. PRAME is a membrane and cytoplasmic protein aberrantly expressed in chronic lymphocytic leukemia and mantle cell lymphoma. Leuk Res. 2006;30(11):1333–39. doi: 10.1016/j.leukres.2006.02.031.
  27. Paydas S, Tanriverdi K, Yavuz S, Seydaoglu G. PRAME mRNA levels in cases with chronic leukemia: Clinical importance and review of the literature. Leuk Res. 2007;31(3):365–9. doi: 10.1016/j.leukres.2006.06.022.
  28. Kawano R, Karube K, Kikuchi M, et al. Oncogene associated cDNA microarray analysis shows PRAME gene expression is a marker for response to anthracycline containing chemotherapy in patients with diffuse large B-cell lymphoma. J Clin Exp Hematop. 2009;49(1):1–7. doi: 10.3960/jslrt.49.1.
  29. Mitsuhashi K, Masuda A, Wang YH, et al. Prognostic significance of PRAME expression based on immunohistochemistry for diffuse large B-cell lymphoma patients treated with R-CHOP therapy. Int J Hematol. 2014;100(1):88–95. doi: 10.1007/s12185-014-1593-z.
  30. Schmitt M, Li L, Giannopoulos K, et al. Chronic myeloid leukemia cells express tumor-associated antigens eliciting specific CD8+ T-cell responses and are lacking costimulatory molecules. Exp Hematol. 2006;34(12):1709–19. doi: 10.1016/j.exphem.2006.07.009.
  31. Qian J, Zhu Z.H, Lin J, et al. Hypomethylation of PRAME promoter is associated with poor prognosis in myelodysplastic syndrome. Br J Haematol. 2011;154(1):153–5. doi: 10.1111/j.1365-2141.2011.08585.x.
  32. Ding K, Wang XM, Fu R, et al. PRAME Gene Expression in Acute Leukemia and Its Clinical Significance. Cancer Biol Med. 2012;9(1):73–6. doi: 10.3969/j.issn.2095-3941.2012.01.013.
  33. Greiner J, Ringhoffer M, Taniguchi M, et al. mRNA expression of leukemia-associated antigens in patients with acute myeloid leukemia for the development of specific immunotherapies. Int J Cancer. 2004;108(5):704–11. doi: 10.1002/ijc.11623.
  34. Li L, Reinhardt P, Schmitt A, et al. Dendritic cells generated from acute myeloid leukemia (AML) blasts maintain the expression of immunogenic leukemia associated antigens. Cancer Immunol Immunother. 2005;54(7):685–93. doi: 10.1007/s00262-004-0631-8.
  35. Atanackovic D, Luetkens T, Kloth B, et al. Cancer-testis antigen expression and its epigenetic modulation in acute myeloid leukemia. Am J Hematol. 2011;86(11):918–22. doi: 10.1002/ajh.22141.
  36. Gerber JM, Qin L, Kowalski J, et al. Characterization of chronic myeloid leukemia stem cells. Am J Hematol. 2011;86(1):31–7. doi: 10.1002/ajh.21915.
  37. Qin YZ, Zhu HH, Liu YR, et al. PRAME and WT1 transcripts constitute a good molecular marker combination for monitoring minimal residual disease in myelodysplastic syndromes. Leuk Lymphoma. 2013;54(7):1442–9. doi: 10.3109/10428194.2012.743656.
  38. Steinbach D, Viehmann S, Zintl F, Gruhn B. PRAME gene expression in childhood acute lymphoblastic leukemia. Cancer Genet Cytogenet. 2002;138(1):89–91. doi: 10.1016/S0165-4608(02)00582-4.
  39. Steinbach D, Hermann J, Viehmann S, et al. Clinical implications of PRAME gene expression in childhood acute myeloid leukemia. Cancer Genet Cytogenet. 2002;133(2):118–23. doi: 10.1016/S0165-4608(01)00570-2.
  40. Spanaki A, Perdikogianni C, Linardakis E, Kalmanti M. Quantitative assessment of PRAME expression in diagnosis of childhood acute leukemia. Leuk Res. 2007;31(5):639–42. doi: 10.1016/j.leukres.2006.06.006.
  41. Steinbach D, Bader P, Willasch A, et al. Prospective Validation of a New Method of Monitoring Minimal Residual Disease in Childhood Acute Myelogenous Leukemia. Clin Cancer Res. 2015;21(6):1353–9. doi: 10.1158/1078-0432.CCR-14-1999.
  42. Paydas S, Tanriverdi K, Yavuz S, et al. PRAME mRNA levels in cases with chronic leukemia: Clinical Importance and Future Prospects. Am J Hematol. 2005;79(4):257–61. doi: 10.1002/ajh.20425.
  43. Steinbach D, Pfaffendorf N, Wittig S, Gruhn B. PRAME expression is not associated with down-regulation of retinoic acid signaling in primary acute myeloid leukemia. Cancer Genet Cytogenet. 2007;177(1):51–4. doi: 10.1016/j.cancergencyto.2007.05.011.
  44. Santamaria C, Chillon MC, Garcia-Sanz R, et al. The relevance of preferentially expressed antigen of melanoma (PRAME) as a marker of disease activity and prognosis in acute promyelocytic leukemia. Haematologica. 2008;93(12):1797–805. doi: 10.3324/haematol.13214.
  45. Qin Y, Zhu H, Jiang B, et al. Expression patterns of WT1 and PRAME in acute myeloid leukemia patients and their usefulness for monitoring minimal residual disease. Leuk Res. 2009;33(3):384–90. doi: 10.1016/j.leukres.2008.08.026.
  46. Мисюрин В.А., Лукина А.Е., Мисюрин А.В. и др. Особенности соотношения уровней экспрессии генов PRAME и PML/RARa в дебюте острого промиелоцитарного лейкоза. Российский биотерапевтический журнал. 2014;13(1):9–16. [Misyurin VA, Lukina AE, Misyurin AV, et al. A ratio between gene expression levels of PRAME and PML/RARA at the onset of acute promyelocytic leukemia and clinical features of the disease. Rossiiskii bioterapevticheskii zhurnal. 2014;13(1):9–16. (In Russ)]
  47. Liberante FG, Pellagatti A, Boncheva V, et al. High and low, but not intermediate, PRAME expression levels are poor prognostic markers in myelodysplastic syndrome at disease presentation. Br J Haematol. 2013;162(2):282–5. doi: 10.1111/bjh.12352.
  48. Goellner S, Steinbach D, Schenk T, et al. Childhood acute myelogenous leukaemia: Association between PRAME, apoptosis- and MDR-related gene expression. Eur J Cancer. 2006;42(16):2807–14. doi: 10.1016/j.ejca.2006.06.018.
  49. Tajeddine N, Louis M, Vermylen C, et al. Tumor associated antigen PRAME is a marker of favorable prognosis in childhood acute myeloid leukemia patients and modifies the expression of S100A4, Hsp 27, p21, IL-8 and IGFBP-2 in vitro and in vivo. Leuk Lymphoma. 2008;49(6):1123–31. doi: 10.1080/10428190802035933.
  50. Santamaria CM, Chillon MC, Garcia-Sanz R, et al. Molecular stratification model for prognosis in cytogenetically normal acute myeloid leukemia. Blood. 2009;114(1):148–52. doi: 10.1182/blood-2008-11-187724.
  51. Ercolak V, Paydas S, Bagir E, et al. PRAME Expression and Its Clinical Relevance in Hodgkin’s Lymphoma. Acta Haematol. 2015;134(4):199–207. doi: 10.1159/000381533.
  52. Luetkens T, Kobold S, Cao Y, et al. Functional autoantibodies against SSX‐2 and NY‐ESO‐1 in multiple myeloma patients after allogeneic stem cell transplantation. Cancer Immunol Immunother. 2014;63(11):1151–62. doi: 10.1007/s00262-014-1588-x.
  53. Gunn SR, Bolla AR, Barron LL, et al. Array CGH analysis of chronic lymphocytic leukemia reveals frequent cryptic monoallelic and biallelic deletions of chromosome 22q11 that include the PRAME gene. Leuk Res. 2009;33(9):1276–81. doi: 10.1016/j.leukres.2008.10.010.
  54. Mraz M, Stano Kozubik K, Plevova K, et al. The origin of deletion 22q11 in chronic lymphocytic leukemia is related to the rearrangement of immunoglobulin lambda light chain locus. Leuk Res. 2013;37(7):802–8. doi: 10.1016/j.leukres.2013.03.018.
  55. Staege MS, Banning-Eichenseer U, Weissflog G, et al. Gene expression profiles of Hodgkin’s lymphoma cell lines with different sensitivity to cytotoxic drugs. Exp Hematol. 2008;36(7):886–96. doi: 10.1016/j.exphem.2008.02.014.
  56. Kewitz S, Staege MS. Knock-Down of PRAME Increases Retinoic Acid Signaling and Cytotoxic Drug Sensitivity of Hodgkin Lymphoma Cells. PLoS One. 2013;8(2):e55897. doi: 10.1371/journal.pone.0055897.
  57. Bea S, Salaverria I, Armengol L, et al. Uniparental disomies, homozygous deletions, amplifications, and target genes in mantle cell lymphoma revealed by integrative high-resolution whole-genome profiling. Blood. 2009;113(13):3059–69. doi: 10.1182/blood-2008-07-170183.
  58. Liggins AP, Lim SH, Soilleux EJ, et al. A panel of cancer-testis genes exhibiting broadspectrum expression in haematological malignancies. Cancer Immun. 2010;10:8.
  59. Radich JP, Dai H, Mao M, et al. Gene expression changes associated with progression and response in chronic myeloid leukemia. Proc Natl Acad Sci USA. 2006;103(8):2794–9. doi: 10.1073/pnas.0510423103.
  60. Luetkens T, Schafhausen P, Uhlich F, et al. Expression, epigenetic regulation, and humoral immunogenicity of cancer-testis antigens in chronic myeloid leukemia. Leuk Res. 2010;34(12):1647–55. doi: 10.1016/j.leukres.2010.03.039.
  61. Hughes A, Clarson J, Tang C, et al. CML patients with deep molecular responses to TKI have restored immune effectors and decreased PD-1 and immune suppressors. Blood. 2017;129(9):1166–76. doi: 10.1182/blood-2016-10-745992.
  62. Khateeb EE, Morgan D. Preferentially Expressed Antigen of Melanoma (PRAME) and Wilms’ Tumor 1 (WT 1) Genes Expression in Childhood Acute Lymphoblastic Leukemia, Prognostic Role and Correlation with Survival. Open Access Maced J Med Sci. 2015;3(1):57–62. doi: 10.3889/oamjms.2015.001.
  63. Zhang YH, Lu AD, Yang L, et al. PRAME overexpression predicted good outcome in pediatric B-cell acute lymphoblastic leukemia patients receiving chemotherapy. Leuk Res. 2017;52):43–9. doi: 10.1016/j.leukres.2016.11.005.
  64. McElwaine S, Mulligan C, Groet J, et al. Microarray transcript profiling distinguishes the transient from the acute type of megakaryoblastic leukaemia (M7) in Down’s syndrome, revealing PRAME as a specific discriminating marker. Br J Haematol. 2004;125(6):729–42. doi: 10.1111/j.1365-2141.2004.04982.x.
  65. Tanaka N, Wang YH, Shiseki M, et al. Inhibition of PRAME expression causes cell cycle arrest and apoptosis in leukemic cells. Leuk Res. 2011;35(9):1219–25. doi: 10.1016/j.leukres.2011.04.005.
  66. De Carvalho D.D, Binato R, Pereira W.O, et al. BCR-ABL-mediated upregulation of PRAME is responsible for knocking down TRAIL in CML patients. Oncogene. 2011;30(2):223–33. doi: 10.1038/onc.2010.409.
  67. Tajeddine N, Gala JL, Louis M, et al. Tumor-associated antigen preferentially expressed antigen of melanoma (PRAME) induces caspase-independent cell death in vitro and reduces tumorigenicity in vivo. Cancer Res. 2005;65(16):7348–55. doi: 10.1158/0008-5472.CAN-04-4011.
  68. Yan H, Zhao RM, Wang ZJ, et al. Knockdown of PRAME enhances adriamycin-induced apoptosis in chronic myeloid leukemia cells. Eur Rev Med Pharmacol Sci. 2015;19(24):4827–34. doi: 10.18632/oncotarget.9977.
  69. Xu Y, Yue Q, Wei H, Pan G. PRAME induces apoptosis and inhibits proliferation of leukemic cells in vitro and in vivo. Int J Clin Exp Pathol. 2015;8(11):14549–55.
  70. Xu Y, Rong LJ, Meng SL, et al. PRAME promotes in vitro leukemia cells death by regulating S100A4/p53 signaling. Eur Rev Med Pharmacol Sci. 2016;20(6):1057–63.
  71. Bullinger L, Schlenk RF, Gotz M, et al. PRAME-Induced Inhibition of Retinoic Acid Receptor Signaling-Mediated Differentiation – Possible Target for ATRA Response in AML without t(15;17). Clin Cancer Res. 2013;19(9):2562–71. doi: 10.1158/1078-0432.CCR-11-2524.

Миелоидные супрессорные клетки при некоторых онкогематологических заболеваниях

А.В. Пономарев

ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 24, Moсква, Российская Федерация, 115478

Для переписки: Александр Васильевич Пономарев, аспирант, Каширское ш., д. 24, Moсква, Российская Федерация, 115478; e-mail: kl8546@yandex.ru

Для цитирования: Пономарев А.В. Миелоидные супрессорные клетки при некоторых онкогематологических заболеваниях. Клиническая онкогематология. 2017;10(1):29–38.

DOI: 10.21320/2500-2139-2017-10-1-29-38


РЕФЕРАТ

Миелоидные супрессорные клетки — это незрелые клетки миелоидного происхождения, обладающие иммуносупрессивными свойствами. В обзоре приведена характеристика миелоидных супрессорных клеток, в т. ч. варианты фенотипа, механизмы супрессивного воздействия на иммунную систему, механизмы рекрутирования опухолью миелоидных супрессоров. Дано краткое описание работ, в которых исследовались миелоидные супрессоры при онкогематологических заболеваниях, включая множественную миелому, лимфомы и лейкозы.

Ключевые слова: миелоидные супрессоры, супрессорные клетки миелоидного происхождения, множественная миелома, лимфомы, лейкозы.

Получено: 8 сентября 2016 г.

Принято в печать: 3 декабря 2016 г.

Читать статью в PDFpdficon


ЛИТЕРАТУРА

  1. Тупицына Д.Н., Ковригина А.М., Тумян Г.С. и др. Клиническое значение внутриопухолевых FOXP3+ Т-регуляторных клеток при солидных опухолях и фолликулярных лимфомах: обзор литературы и собственные данные. Клиническая онкогематология. 2012;(5)3:193–203. [Tupitsyna DN, Kovrigina AM, Tumian GS, et al. Different clinical meaning of intratumoral FOXP3+ T-regulatory cells in solid tumors and follicular lymphomas: literature review and own data. Klinicheskaya onkogematologiya. 2012;(5)3:193–203. (In Russ)]
  2. Кадагидзе З.Г., Черткова А.И., Славина Е.Г. NKT-клетки и противоопухолевый иммунитет. Российский биотерапевтический журнал. 2011;10(3):9–16. [Kadagidze ZG, Chertkova AI, Slavina EG. NKT-cells and antitumor immunity. Rossiiskii bioterapevticheskii zhurnal. 2011;10(3):9–16. (In Russ)]
  3. Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev 2012;12(4):253–68. doi: 10.1038/nri3175.
  4. Gabrilovich DI, Bronte V, Chen S-H, et al. The terminology issue for myeloid-derived suppressor cells. Cancer Res. 2007;67(1):425– doi: 10.1158/0008-5472.CAN-06-3037.
  5. Bowen JL, Olson JK. Innate immune CD11b+Gr-1+ cells, suppressor cells, affect the immune response during Theiler’s virus-induced demyelinating disease. J Immunol. 2009;183(11):6971–80. doi: 10.4049/jimmunol.0902193.
  6. Tsiganov EN, Verbina EM, Radaeva TV, et al. Gr-1dim CD11b+ immature myeloid-derived suppressor cells but not neutrophils are markers of lethal tuberculosis infection in mice. J Immunol. 2014;192(10):4718–27. doi: 10.4049/jimmunol.1301365.
  7. Delano MJ, Scumpia PO, Weinstein JS, et al. MyD88-dependent expansion of an immature GR-1(+)CD11b(+) population induces T cell suppression and Th2 polarization in sepsis. J Exp Med. 2007;204(6):1463–74.
  8. Гапонов М.А., Хайдуков С.В., Писарев В.М. и др. Субпопуляционная гетерогенность миелоидных иммуносупрессорных клеток у пациентов с септическими состояниями. Российский иммунологический журнал. 2015;9(18):11–14. [Gaponov MA, Khaidukov SV, Pisarev VM, et al. Subpopulation heterogeneity of immunosuppressive myeloid cells in patients with sepsis. Rossiiskii immunologicheskii zhurnal. 2015;9(18):11–14. (In Russ)]
  9. Makarenkova VP, Bansal V, Matta BM, et al. CD11b+/Gr-1+ myeloid suppressor cells cause T cell dysfunction after traumatic stress. J Immunol. 2006;176(4):2085–94. doi: 10.4049/jimmunol.176.4.2085.
  10. Greten TF, Manns MP, Korangy F. Myeloid derived suppressor cells in human diseases. Int. 2011;11(7):802–7. doi: 10.1016/j.intimp.2011.01.003.
  11. Diaz-Montero CM, Salem ML, Nishimura MI, 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. doi: 10.1007/s00262-008-0523-
  12. Yazdani Y, Mohammadnia-Afrouzi M, Yousefi M, et al. Myeloid-derived suppressor cells in B cell malignancies. Tumour Biol. 2015;36(10):7339–53. doi: 10.1007/s13277-015-4004-z.
  13. Пономарев А.В. Миелоидные супрессорные клетки: общая характеристика. Иммунология. 2016;37(1):47–50. doi: 10.18821/0206-4952-2016-37-1-47-50. [Ponomarev AV. Myeloid suppressor cells: general characteristics. Immunologiya. 2016;37(1):47–50. doi: 10.18821/0206-4952-2016-37-1-47- (In Russ)]
  14. Gabrilovich DI, Nagaraj S. Myeloid-derived-suppressor cells as regulators of the immune system. Nat Rev Immunol. 2009;9(3):162–74. doi: 10.1038/nri2506.
  15. Lechner MG, Megiel C, Russell SM, et al. Functional characterization of human Cd33+ And Cd11b+ myeloid-derived suppressor cell subsets induced from peripheral blood mononuclear cells co-cultured with a diverse set of human tumor cell lines. J Transl 2011;9(1):90. doi: 10.1186/1479-5876-9-90.
  16. Rodriguez PC, Ernstoff MS, Hernandez C, et al. Arginase I–Producing Myeloid-Derived Suppressor Cells in Renal Cell Carcinoma Are a Subpopulation of Activated Granulocytes. Cancer Res. 2009;69(4):1553–60.
  17. Schmielau J, Finn OJ. Activated granulocytes and granulocyte-derived hydrogen peroxide are the underlying mechanism of suppression of T-cell function in advanced cancer patients. Cancer Res. 2001;61(12):4756–60.
  18. Youn J-I, Collazo M, Shalova I, et al. Characterization of the nature of granulocytic myeloid-derived suppressor cells in tumor-bearing mice. J Leuk 2012;91(1):167–81. doi: 10.1189/jlb.0311177.
  19. Youn J-I, Nagaraj S, Collazo M, et al. Subsets of Myeloid-Derived Suppressor Cells in Tumor Bearing Mice. J Immunol. 2008;181(8):5791–802. doi: 10.4049/jimmunol.181.8.5791.
  20. Corzo CA, Condamine T, Lu L, et al. HIF-1alpha regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment. J Exp Med. 2010;207(11):2439–53. doi: 10.1084/jem.20100587.
  21. Yang L, DeBusk LM, Fukuda K, et al. Expansion of myeloid immune suppressor Gr+CD11b+ cells in tumor-bearing host directly promotes tumor angiogenesis. Cancer Cell. 2004;6(4):409–21. doi: 10.1016/j.ccr.2004.08.031.
  22. Zhuang J, Zhang J, Lwin ST, et al. Osteoclasts in multiple myeloma are derived from Gr-1+CD11b+ myeloid-derived suppressor cells. PLoS One. 2012;7(11):e48871. doi: 1371/journal.pone.0048871.
  23. Choi J, Suh B, Ahn YO, et al. CD15+/CD16low human granulocytes from terminal cancer patients: granulocytic myeloid-derived suppressor cells that have suppressive function. Tumour Biol. 2012;33(1):121–9. doi: 10.1007/s13277-011-0254-
  24. Stanojevic I, Miller K, Kandolf-Sekulovic L, et al. A subpopulation that may correspond to granulocytic myeloid-derived suppressor cells reflects the clinical stage and progression of cutaneous melanoma. Int Immunol. 2016;28(2):87–97. doi: 10.1093/intimm/dxv053.
  25. Saiwai H, Kumamaru H, Ohkawa Y, et al. Ly6C+Ly6G– Myeloid-derived suppressor cells play a critical role in the resolution of acute inflammation and the subsequent tissue repair process after spinal cord injury. J Neurochem. 2013;125(1):74–88. doi: 10.1111/jnc.12135.
  26. Rodriguez PC, Augusto CO. Arginine regulation by myeloid derived suppressor cells and tolerance in cancer: mechanisms and therapeutic perspectives. Immunol 2008;222(1):180–91. doi: 10.1111/j.1600-065X.2008.00608.x.
  27. Srivastava MK, Sinha P, Clements VK, et al. Myeloid-derived suppressor cells inhibit T cell activation by depleting cystine and cysteine. Cancer Res. 2010;70(1):68–77. doi: 10.1158/0008-CAN-09-2587.
  28. Chevolet I, Speeckaert R, Schreuer M, et al. Characterization of the in vivo immune network of IDO, tryptophan metabolism, PD-L1, and CTLA-4 in circulating immune cells in melanoma. Oncoimmunology. 2015;4(3):e982382. doi: 10.4161/2162402X.2014.982382.
  29. Jitschin R, Braun M, Buttner M, et al. CLL-cells induce IDOhiCD14+HLA-DRlo myeloid-derived suppressor cells that inhibit T-cell responses and promote Tregs. Blood. 2014;124(5):750–60. doi: 10.1182/blood-2013-12-
  30. Nagaraj S, Gupta K, Pisarev V, et al. Altered recognition of antigen is a mechanism of CD8+ T cell tolerance in cancer. Nat Med. 2007;13(7):828–35. doi: 10.1038/nm1609.
  31. Lu T, Ramakrishnan R, Altiok S, et al. Tumor-infiltrating myeloid cells induce tumor cell resistance to cytotoxic T cells in mice. J Clin 2011;121(10):4015–4029. doi: 10.1172/JCI45862.
  32. Hanson EM, Clements VK, Sinha P, et al. Myeloid-derived suppressor cells down-regulate L-selectin expression on CD4+ and CD8+ T cells. J. Immunol. 2009;183(2):937–44. doi: 10.4049/jimmunol.0804253.
  33. Noman MZ, Desantis G, Janji B, et al. PD-L1 is a novel direct target of HIF-1a, and its blockade under hypoxia enhanced MDSC-mediated T cell activation. J Exp Med. 2014;211(5):781–90. doi: 10.1084/jem.20131916.
  34. Filipazzi P, Valenti R, Huber V, 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):2546–53. doi: 10.1200/JCO.2006.08.5829.
  35. Sinha P, Clements VK, Bunt SK, et al. Cross-talk between myeloid-derived suppressor cells and macrophages subverts tumor immunity toward a type 2 response. J Immunol. 2007;179(2):977–83. doi: 10.4049/jimmunol.179.2.977.
  36. Li H, Han Y, Guo Q, et al. Cancer-expanded myeloid-derived suppressor cells induce anergy of NK cells through membrane-bound TGF-beta 1. J Immunol. 2009;182(1):240–9. doi: 10.4049/jimmunol.182.1.240.
  37. Liu C, Yu S, Kappes J, et al. Expansion of spleen myeloid suppressor cells represses NK cell cytotoxicity in tumor-bearing host. Blood. 2007;109(10):4336–42. doi: 10.1182/blood-2006-09-
  38. Elkabets M, Ribeiro VSG, Dinarello CA, et al. IL-1b regulates a novel myeloid-derived suppressor cell subset that impairs NK cell development and function. Eur J Immunol. 2010;40(12):3347–57. doi: 10.1002/eji.201041037.
  39. Hoechst B, Voigtlaender T, Ormandy L, et al. Myeloid derived suppressor cells inhibit natural killer cells in patients with hepatocellular carcinoma via the NKp30 receptor. Hepatology. 2009;50(3):799–807. doi: 10.1002/hep.23054.
  40. Pan PY, Ma G, Weber KJ, et al. 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;70(1):99–108. doi: 10.1158/0008-CAN-09-1882.
  41. Hoechst B, Gamrekelashvili J, Manns MP, et al. Plasticity of human Th17 cells and iTregs is orchestrated by different subsets of myeloid cells. Blood. 2011;117(24):6532–41. doi: 10.1182/blood-2010-11-
  42. Shojaei F, Wu X, Malik AK, et al. Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells. Nat Biotechnol. 2007;25(8):911–20. doi: 10.1038/nbt1323.
  43. Connolly MK, Mallen-St Clair J, Bedrosian AS, et al. Distinct populations of metastases-enabling myeloid cells expand in the liver of mice harboring invasive and preinvasive intra-abdominal tumor. J Leuk Biol. 2010;87(4):713–25. doi: 10.1189/jlb.0909607.
  44. Yang L, Huang J, Ren X, et al. Abrogation of TGFb signaling in mammary carcinomas recruits Gr-1+CD11b+ myeloid cells that promote metastasis. Cancer Cell. 2008;13(1):23–35. doi: 10.1016/j.ccr.2007.12.004.
  45. Giles A, Vicioso Y, Kasai M, et al. Bone marrow-derived progenitor cells develop into myeloid-derived suppressor cells at metastatic sites. J Immunother Cancer. 2013;1(Suppl 1):188. doi: 10.1186/2051-1426-1-S1-P188.
  46. Solito S, Falisi E, Diaz-Montero CM, et al. A human promyelocytic-like population is responsible for the immune suppression mediated by myeloid-derived suppressor cells. Blood. 2011;118(8):2254–65. doi: 10.1182/blood-2010-12-
  47. Marigo I, Bosio E, Solito S, et al. Tumor-induced tolerance and immune suppression depend on the C/EBPbeta transcription factor. Immunity. 2010;32(6):790–802. doi: 10.1016/j.immuni.2010.05.010.
  48. Highfill SL, Rodriguez PC, Zhou Q, et al. Bone marrow myeloid-derived suppressor cells (MDSCs) inhibit graft-versus-host disease (GVHD) via an arginase-1-dependent mechanism that is up-regulated by interleukin-13. Blood. 2010;116(25):5738–47. doi: 10.1182/blood-2010-06-
  49. Lechner MG, Liebertz DJ, Epstein AL. Characterization of cytokine-induced myeloid derived suppressor cells from normal human peripheral blood mononuclear cells. J Immunol. 2010;185(4):2273–84. doi: 10.4049/jimmunol.1000901.
  50. Atretkhany KS, Nosenko MA, Gogoleva VS, et al. TNF Neutralization Results in the Delay of Transplantable Tumor Growth and Reduced MDSC Accumulation. Front Immunol. 2016;7:147. doi: 10.3389/fimmu.2016.00147.
  51. De Veirman K, Van Valckenborgh E, Lahmar Q, et al. Myeloid-derived suppressor cells as therapeutic target in hematological malignancies. Front Oncol. 2014;4:349. doi: 10.3389/fonc.2014.00349.
  52. Ramachandran I, Martner A, Pisklakova A, et al. Myeloid-derived suppressor cells regulate growth of multiple myeloma by inhibiting T cells in bone marrow. J Immunol. 2013;190(7):3815–23. doi: 10.4049/jimmunol.1203373.
  53. De Veirman K, Van Ginderachter JA, Lub S, et al. Multiple myeloma induces Mcl-1 expression and survival of myeloid-derived suppressor cells. Oncotarget. 2015;6(12):10532–47. doi: 10.18632/oncotarget.3300.
  54. Brimnes MK, Vangsted AJ, Knudsen LM, et al. Increased level of both CD4+FOXP3+ regulatory T cells and CD14+HLA-DR/low myeloid-derived suppressor cells and decreased level of dendritic cells in patients with multiple myeloma. Scand J Immunol. 2010;72(6):540–7. doi: 10.1111/j.1365-2010.02463.x.
  55. Gorgun GT, Whitehill G, Anderson JL, et al. Tumor-promoting immune-suppressive myeloid-derived suppressor cells in the multiple myeloma microenvironment in humans. Blood. 2013;121(15):2975–87. doi: 10.1182/blood-2012-08-
  56. Gorgun GТ, Samur MK, Cowens KB, et al. Lenalidomide Enhances Immune Checkpoint Blockade-Induced Immune Response in Multiple Myeloma. Clin Cancer Res. 2015;21(20):4607–18. doi: 10.1158/1078-CCR-15-0200.
  57. Busch A, Zeh D, Janzen V, et al. Treatment with lenalidomide induces immuno-activating and counter-regulatory immunosuppressive changes in myeloma patients. Clin Exp Immunol. 2014;177(2):439–53. doi: 10.1111/cei.12343.
  58. Wang Z, Zhang L, Wang H, et al. Tumor-induced CD14+HLA-DR (-/low) myeloid-derived suppressor cells correlate with tumor progression and outcome of therapy in multiple myeloma patients. Cancer Immunol Immunother. 2015;64(3):389–99. doi: 10.1007/s00262-014-1646-
  59. De Keersmaecker B, Fostier K, Corthals J, et al. Immunomodulatory drugs improve the immune environment for dendritic cell-based immunotherapy in multiple myeloma patients after autologous stem cell transplantation. Cancer Immunol Immunother. 2014;63(10):1023–36. doi: 10.1007/s00262-014-1571-
  60. Castella B, Foglietta M, Sciancalepore P, et al. Anergic bone marrow Vg9Vd2 T cells as early and long-lasting markers of PD-1-targetable microenvironment-induced immune suppression in human myeloma. Oncoimmunology. 2015;4(11):e1047580. doi: 10.1080/2162402X.2015.1047580.
  61. Giallongo C, Tibullo D, Parrinello NL, et al. Granulocyte-like myeloid derived suppressor cells (G-MDSC) are increased in multiple myeloma and are driven by dysfunctional mesenchymal stem cells (MSC). Oncotarget. 2016;7(52):85764– doi: 10.18632/oncotarget.7969.
  62. Lee SE, Lim JY, Ryu DB, et al. Circulating immune cell phenotype can predict the outcome of lenalidomide plus low-dose dexamethasone treatment in patients with refractory/relapsed multiple myeloma. Cancer Immunol Immunother. 2016;65(8):983–94. doi: 10.1007/s00262-016-1861-
  63. Favaloro J, Liyadipitiya T, Brown R, et al. Myeloid derived suppressor cells are numerically, functionally and phenotypically different in patients with multiple myeloma. Leuk Lymphoma. 2014;55(12):2893–900. doi: 10.3109/10428194.2014.904511.
  64. Franssen LE, van de Donk NW, Emmelot ME, et al. The impact of circulating suppressor cells in multiple myeloma patients on clinical outcome of DLIs. Bone Marrow Transplant. 2015;50(6):822–8. doi: 10.1038/bmt.2015.48.
  65. Lin Y, Gustafson MP, Bulur PA, et al. Immunosuppressive CD14+HLA-DRlow/– monocytes in B-cell non-Hodgkin lymphoma. Blood. 2011;117(3):872–81. doi: 10.1182/blood-2010-05-
  66. Tadmor T, Fell R, Polliack A, et al. Absolute monocytosis at diagnosis correlates with survival in diffuse large B-cell lymphoma—possible link with monocytic myeloid-derived suppressor cells. Hematol 2013;31(2):65–71. doi: 10.1002/hon.2019.
  67. Gustafson MP, Lin Y, LaPlant B, et al. Immune monitoring using the predictive power of immune profiles. J Immunother Cancer. 2013;1(1):7. doi: 10.1186/2051-1426-1-7.
  68. Wu C, Wu X, Zhang X, et al. Prognostic significance of peripheral monocytic myeloid-derived suppressor cells and monocytes in patients newly diagnosed with diffuse large B-cell lymphoma. Int J Clin Exp Med. 2015;8(9):15173–81.
  69. Sato Y, Shimizu K, Shinga J, et al. Characterization of the myeloid-derived suppressor cell subset regulated by NK cells in malignant lymphoma. Oncoimmunology. 2015;4(3):e995541. doi: 10.1080/2162402X.2014.995541.
  70. Romano A, Parrinello NL, Vetro C, et al. Circulating myeloid-derived suppressor cells correlate with clinical outcome in Hodgkin Lymphoma patients treated up-front with a risk-adapted strategy. Br J Haematol. 2015;168(5):689–700. doi: 10.1111/bjh.13198.
  71. Marini O, Spina C, Mimiola E, et al. Identification of granulocytic myeloid-derived suppressor cells (G-MDSCs) in the peripheral blood of Hodgkin and non-Hodgkin lymphoma patients. Oncotarget. 2016;19(7):27677–88. doi: 10.18632/oncotarget.8507.
  72. Azzaoui I, Uhel F, Rossille D, et al. T-cell defect in diffuse large B-cell lymphomas involves expansion of myeloid derived suppressor cells expressing IL-10, PD-L1 and S100A12. Blood. 2016;128(8):1081–92. doi: 10.1182/blood-2015-08-
  73. Zhang H, Li ZL, Ye SB, et al. Myeloid-derived suppressor cells inhibit T cell proliferation in human extranodal NK/T cell lymphoma: a novel prognostic indicator. Cancer Immunol Immunother. 2015;64(12):1587- doi: 10.1007/s00262-015-1765-6.
  74. Christiansson L, Sоderlund S, Svensson E, et al. Increased Level of Myeloid-Derived Suppressor Cells, Programmed Death Receptor Ligand 1/Programmed Death Receptor 1, and Soluble CD25 in Sokal High Risk Chronic Myeloid Leukemia. PLoS One. 2013;8(1):e55818. doi: 10.1371/journal.pone.0055818.
  75. Giallongo C, Romano A, Parrinello NL, et al. Mesenchymal Stem Cells (MSC) Regulate Activation of Granulocyte-Like Myeloid Derived Suppressor Cells (G-MDSC) in Chronic Myeloid Leukemia Patients. PLoS One. 2016;11(7):e0158392. doi: 10.1371/journal.pone.0158392.
  76. Gustafson МP, Abraham RS, Lin Y, et al. Association of an increased frequency of CD14+HLA-DRlo/neg monocytes with decreased time to progression in chronic lymphocytic leukaemia (CLL). Br J Haematol. 2012;156(5):674–6. doi: 10.1111/j.1365-2011.08902.x.
  77. Liu J, Zhou Y, Huang Q, et al. CD14+HLA-DRlow/– expression: a novel prognostic factor in chronic lymphocytic leukemia. Oncol 2015;9(3):1167–72. doi: 10.3892/ol.2014.2808.
  78. Sun H, Li Y, Zhang ZF, et al. Increase in myeloid-derived suppressor cells (MDSCs) associated with minimal residual disease (MRD) detection in adult acute myeloid leukemia. Int J Hematol. 2015;102(5):579–86. doi: 10.1007/s12185-015-1865-
  79. Gleason MK, Ross JA, Warlick ED, et al. CD16xCD33 bispecific killer cell engager (BiKE) activates NK cells against primary MDS and MDSC CD33+ targets. Blood. 2014;123(19):3016–26. doi: 10.1182/blood-2013-10-
  80. Chen X, Eksioglu EA, Zhou J, et al. Induction of myelodysplasia by myeloid-derived suppressor cells. J Clin Invest. 2013;123(11):4595–611. doi: 10.1172/JCI67580.
  81. Kittang AO, Kordasti S, Sand KE, et al. Expansion of myeloid derived suppressor cells correlates with number of T regulatory cells and disease progression in myelodysplastic syndrome. Oncoimmunology. 2015;5(2):e1062208. doi: 10.1080/2162402X.2015.1062208.
  82. Noonan KA, Ghosh N, Rudraraju L, et al. Targeting immune suppression with PDE5 inhibition in end-stage multiple myeloma. Cancer Immunol Res. 2014;2(8):725–31. doi: 10.1158/2326-CIR-13-0213.