Субпопуляционный состав T-хелперов у больных острыми лейкозами после трансплантации аллогенных гемопоэтических стволовых клеток

Ю.О. Давыдова, Н.М. Капранов, К.А. Никифорова, О.С. Караваева, Д.В. Камельских, М.Ю. Дроков, Л.А. Кузьмина, Т.В. Гапонова, И.В. Гальцева, Е.Н. Паровичникова

ФГБУ «НМИЦ гематологии» Минздрава России, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167

Для переписки: Юлия Олеговна Давыдова, канд. мед. наук, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167; тел.: +7(499)612-62-21; e-mail: davydova.y@blood.ru

Для цитирования: Давыдова Ю.О., Капранов Н.М., Никифорова К.А. и др. Субпопуляционный состав T-хелперов у больных острыми лейкозами после трансплантации аллогенных гемопоэтических стволовых клеток. Клиническая онкогематология. 2023;16(2):137–45.

DOI: 10.21320/2500-2139-2023-16-2-137-145


РЕФЕРАТ

Цель. Выявить особенности субпопуляционного состава Т-хелперов у здоровых доноров и сравнить полученные данные с таковыми у пациентов с острыми лейкозами через 6 мес. после трансплантации аллогенных гемопоэтических стволовых клеток (аллоТГСК).

Материалы и методы. В исследование включены 41 донор крови и 49 пациентов после проведения аллоТГСК. Медиана возраста доноров составила 36 лет (диапазон 20–60 лет), мужчин было 29, женщин — 12. Медиана возраста пациентов составила 37 лет (диапазон 19–62 года), мужчин было 18, женщин — 31. Острый миелоидный лейкоз диагностирован у 27 (55 %) пациентов, острый лимфобластный лейкоз/лимфома — у 22 (45 %). Миелоаблативное кондиционирование проведено у 4 (8 %) пациентов, кондиционирование со сниженной интенсивностью — у 45 (92 %). Субпопуляционный состав Т-хелперов изучен в крови у здоровых доноров и пациентов с острыми лейкозами после аллоТГСК. С помощью проточной цитометрии одновременно оценивали экспрессию маркеров CD3, CD4, CD8, CD25, CD45RA, CD197, CD28, CCR4, CCR6, CCR10, CXCR3, CXCR5 на T-клетках.

Результаты. Показано, что число Т-хелперов, находящихся на разных стадиях дифференцировки (регуляторных, наивных T-клеток, клеток памяти, эффекторных клеток), комплексно отличает здоровых доноров от пациентов. Кроме того, функциональный состав каждой из этих популяций отличает доноров от пациентов даже на +6-м месяце после аллоТГСК. Среди T-хелперов центральной памяти число поляризованных клеток было выше у доноров. У пациентов оказалась выше доля T-хелперов 1-го типа среди эффекторных клеток.

Заключение. Полученные результаты указывают на то, что анализ Т-клеток в комплексе параметров может быть применен для оценки иммунитета и описания его нарушений при различных патологических состояниях или после противоопухолевого лекарственного воздействия.

Ключевые слова: проточная цитометрия, Т-клетки, Т-хелперы, доноры крови, субпопуляции лимфоцитов.

Получено: 26 октября 2022 г.

Принято в печать: 10 марта 2023 г.

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ЛИТЕРАТУРА

  1. Lugli E, Pinti M, Nasi M, et al. Subject classification obtained by cluster analysis and principal component analysis applied to flow cytometric data. Cytom Part A. 2007;71(5):334–44. doi: 10.1002/CYTO.A.20387.
  2. Shevyrev D, Tereshchenko V. Treg Heterogeneity, Function, and Homeostasis. Front Immunol. 2020;10:3100. doi: 10.3389/FIMMU.2019.03100/BIBTEX.
  3. Mahnke YD, Brodie TM, Sallusto F, et al. The who’s who of T-cell differentiation: Human memory T-cell subsets. Eur J Immunol. 2013;43(11):2797–809. doi: 10.1002/eji.201343751.
  4. Hammarlund E, Lewis MW, Hansen SG, et al. Duration of antiviral immunity after smallpox vaccination. Nat Med. 2003;9(9):1131–7. doi: 10.1038/NM917.
  5. Dawes R, Petrova S, Liu Z, et al. Combinations of CD45 Isoforms Are Crucial for Immune Function and Disease. J Immunol. 2006;176(6):3417. doi: 10.4049/JIMMUNOL.176.6.3417.
  6. Gattinoni L, Lugli E, Ji Y, et al. A human memory T-cell subset with stem cell-like properties. Nat Med. 2011;17(10):1290. doi: 10.1038/NM.2446.
  7. Lugli E, Dominguez MH, Gattinoni L, et al. Superior T memory stem cell persistence supports long-lived T cell memory. J Clin Invest. 2013;123(2):594. doi: 10.1172/JCI66327.
  8. Romero P, Zippelius A, Kurth I, et al. Four Functionally Distinct Populations of Human Effector-Memory CD8+ T Lymphocytes. J Immunol. 2007;178(7):4112–9. doi: 10.4049/JIMMUNOL.178.7.4112.
  9. Bonecchi R, Bianchi G, Bordignon PP, et al. Differential Expression of Chemokine Receptors and Chemotactic Responsiveness of Type 1 T Helper Cells (Th1s) and Th2s. J Exp Med. 1998;187(1):129–34. doi: 10.1084/JEM.187.1.129.
  10. Duhen T, Geiger R, Jarrossay D, et al. Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells. Nat Immunol. 2009;10(8):857–63. doi: 10.1038/ni.1767.
  11. Rivino L, Messi M, Jarrossay D, et al. Chemokine Receptor Expression Identifies Pre–T Helper (Th)1, Pre–Th2, and Nonpolarized Cells among Human CD4+ Central Memory T Cells. J Exp Med. 2004;200(6):725–35. doi: 10.1084/JEM.20040774.
  12. Acosta-Rodriguez EV, Rivino L, Geginat J, et al. Surface phenotype and antigenic specificity of human interleukin 17–producing T helper memory cells. Nat Immunol. 2007;8(6):639–46. doi: 10.1038/ni1467.
  13. Zhang N, Pan HF, Ye DQ. Th22 in inflammatory and autoimmune disease: prospects for therapeutic intervention. Mol Cell Biochem. 2011;353(1):41–6. doi: 10.1007/S11010-011-0772-Y.
  14. Bunjun R, Omondi FMA, Makatsa MS, et al. Th22 Cells Are a Major Contributor to the Mycobacterial CD4+ T Cell Response and Are Depleted During HIV Infection. J Immunol. 2021;207(5):1239–49. doi: 10.4049/JIMMUNOL.1900984.
  15. Beilhack A, Schulz S, Baker J, et al. In vivo analyses of early events in acute graft-versus-host disease reveal sequential infiltration of T-cell subsets. Blood. 2005;106(3):1113–22. doi: 10.1182/blood-2005-02-0509.
  16. Wysocki CA, Panoskaltsis-Mortari A, Blazar BR, Serody JS. Leukocyte migration and graft-versus-host disease. Blood. 2005;105(11):4191–9. doi: 10.1182/blood-2004-12-4726.
  17. Попова Н.Н, Савченко В.Г. Реконституция Т-клеточного звена иммунной системы у больных после трансплантации аллогенных гемопоэтических стволовых клеток. Гематология и трансфузиология. 2020;65(1):24–38. doi: 10.35754/0234-5730-2020-65-1-24-38.
    [Popova NN, Savchenko VG. Reconstitution of T-cell-mediated immunity in patients after allogeneic stem cell transplantation. Russian journal of hematology and transfusiology. 2020;65(1):24–38. doi: 10.35754/0234-5730-2020-65-1-24-38. (In Russ)]
  18. Ringhoffer S, Rojewski M, Dohner H, et al. T-cell reconstitution after allogeneic stem cell transplantation: assessment by measurement of the sjTREC/βTREC ratio and thymic naive T cells. Haematologica. 2013;98(10):1600–8. doi: 10.3324/haematol.2012.072264.
  19. Pei X, Zhao X, Wang Y, et al. Comparison of reference values for immune recovery between event-free patients receiving haploidentical allografts and those receiving human leukocyte antigen-matched sibling donor allografts. Front Med. 2017;12(2):153–63. doi: 10.1007/S11684-017-0548-1.
  20. Благов С.Л., Шелихова Л.Н., Осипова Е.Ю. и др. Применение инфузий T-клеток памяти с целью профилактики вирусных инфекций у пациентов с гемобластозами, перенесших аллогенную трансплантацию гемопоэтических стволовых клеток с деплецией альфа/бета Т-лимфоцитов. Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2018;17(2):9–20.
    [Blagov SL, Shelikhova LN, Osipova EYu, et al. Low dose donor memory T-cell infusion after TCR alpha/beta depleted stem cell transplantation for patients with malignant disorders. Voprosy gematologii/onkologii i immunopatologii v pediatrii. 2018;17(2):9–20. (In Russ)]
  21. Mahnke YD, Beddall MH, Roederer M. OMIP-017: Human CD4+ Helper T-cell Subsets Including Follicular Helper Cells. Cytometry A. 2013;83(5):439. doi: 10.1002/CYTO.A.22269.
  22. Spadea M, Saglio F, Tripodi SI, et al. Multivariate Analysis of Immune Reconstitution and Relapse Risk Scoring in Children Receiving Allogeneic Stem Cell Transplantation for Acute Leukemias. Transplant Direct. 2021;7(11):e774. doi: 10.1097/TXD.0000000000001226.
  23. Mackall CL, Fleisher TA, Brown MR, et al. Age, thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy. N Engl J Med. 1995;332(3):143–9. doi: 10.1056/NEJM199501193320303.
  24. Hakim FT, Memon SA, Cepeda R, et al. Age-dependent incidence, time course, and consequences of thymic renewal in adults. J Clin Invest. 2005;115(4):930–9. doi: 10.1172/JCI22492.
  25. Van Den Brink MRM, Velardi E, Perales MA. Immune reconstitution following stem cell transplantation. Hematol Am Soc Hematol Educ Progr. 2015;2015(1):215–9. doi: 10.1182/asheducation-2015.1.215.
  26. Dean HF, Cazaly A, Hurlock C, et al. Defects in lymphocyte subsets and serological memory persist a median of 10 years after high-dose therapy and autologous progenitor cell rescue for malignant lymphoma. Bone Marrow Transplant. 2012;47(12):1545–51. doi: 10.1038/bmt.2012.73.
  27. Chung B, Barbara-Burnham L, Barsky L, Weinberg K. Radiosensitivity of thymic interleukin-7 production and thymopoiesis after bone marrow transplantation. Blood. 2001;98(5):1601–6. doi: 10.1182/blood.V98.5.1601.
  28. Mackall CL, Fleisher TA, Brown MR, et al. Distinctions Between CD8+ and CD4+ T-Cell Regenerative Pathways Result in Prolonged T-Cell Subset Imbalance After Intensive Chemotherapy. Blood. 1997;89(10):3700–7. doi: 10.1182/blood.V89.10.3700.
  29. Poulin JF, Sylvestre M, Champagne P, et al. Evidence for adequate thymic function but impaired naive T-cell survival following allogeneic hematopoietic stem cell transplantation in the absence of chronic graft-versus-host disease. Blood. 2003;102(13):4600–7. doi: 10.1182/blood-2003-05-1428.
  30. Wang YT, Kong Y, Song Y, et al. Increased Type 1 Immune Response in the Bone Marrow Immune Microenvironment of Patients with Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2016;22(8):1376–82. doi: 10.1016/J.BBMT.2016.04.016.
  31. Monteiro JP, Bonomo A. Linking immunity and hematopoiesis by bone marrow T cell activity. Brazilian J Med Biol Res. 2005;38(10):1475–86. doi: 10.1590/S0100-879X2005001000004.
  32. Monteiro JP, Benjamin A, Costa ES, et al. Normal hematopoiesis is maintained by activated bone marrow CD4+ T cells. Blood. 2005;105(4):1484–91. doi: 10.1182/blood-2004-07-2856.
  33. Bonomo A, Monteiro AC, Goncalves-Silva T, et al. A T cell view of the bone marrow. Front Immunol. 2016;7:184. doi: 10.3389/FIMMU.2016.00184/BIBTEX.
  34. Yang YG, Dey BR, Sergio JJ, et al. Donor-derived interferon gamma is required for inhibition of acute graft-versus-host disease by interleukin 12. J Clin Invest. 1998;102(12):2126–35. doi: 10.1172/JCI4992.
  35. Engelhardt BG, Paczesny S, Jung DK, et al. Early Th1 immunity promotes immune tolerance and may impair graft-versus-leukemia effect after allogeneic hematopoietic cell transplantation. Haematologica. 2016;101(5):e204–e208. doi: 10.3324/haematol.2015.139501.
  36. Brok HPM, Vossen JM, Heidt PJ. Interferon-γ-mediated prevention of graft-versus-host disease: Development of immune competent and allo-tolerant T cells in chimeric mice. Bone Marrow Transplant. 1997;19(6):601–6. doi: 10.1038/SJ.BMT.1700707.
  37. Carlson MJ, West ML, Coghill JM, et al. In vitro–differentiated TH17 cells mediate lethal acute graft-versus-host disease with severe cutaneous and pulmonary pathologic manifestations. Blood. 2009;113(6):1365–74. doi: 10.1182/blood-2008-06-162420.
  38. Crane IJ, Forrester JV. Th1 and Th2 Lymphocytes in Autoimmune Disease. Crit Rev Immunol. 2005;25(2):75–102. doi: 10.1615/critrevimmunol.V25.I2.10.

Морфо-иммуногистохимические особенности различных стадий грибовидного микоза: обзор литературы

А.А. Шерстнев, А.М. Ковригина

ФГБУ «НМИЦ гематологии» Минздрава России, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167

Для переписки: Андрей Алексеевич Шерстнев, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167; e-mail: sherstnevandrejj@mail.ru

Для цитирования: Шерстнев А.А., Ковригина А.М. Морфо-иммуногистохимические особенности различных стадий грибовидного микоза: обзор литературы. Клиническая онкогематология. 2023;16(2):109–18.

DOI: 10.21320/2500-2139-2023-16-2-109-118


РЕФЕРАТ

Грибовидный микоз (ГМ) — наиболее распространенный вариант Т-клеточной лимфомы кожи. Патогенез ГМ до настоящего времени полностью не изучен. Дифференциальная диагностика заболевания, в особенности на ранних стадиях, сложна и представляет серьезную задачу. В настоящем обзоре литературы освещаются современные представления о патогенезе ГМ и методах диагностики данного заболевания.

Ключевые слова: грибовидный микоз, наивные Т-клетки, Т-хелперы, реактивное микроокружение.

Получено: 21 сентября 2022 г.

Принято в печать: 3 марта 2023 г.

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ЛИТЕРАТУРА

  1. Кохан М.М. Т-клеточные злокачественные лимфомы кожи: клинические и иммунологические аспекты диагностики, стадийного течения и терапии: Автореф. … д-ра мед. наук. М., 2002.
    [Kokhan MM. T-kletochnye zlokachestvennye limfomy kozhi: klinicheskie i immunologicheskie aspekty diagnostiki, stadiinogo techeniya i terapii. (Cutaneous T-cell malignant lymphomas: clinical and immunological aspects of diagnosis, stage course, and therapy.) [dissertation] Moscow; 2002. (In Russ)]
  2. Willemze R, Jaffe ES, Burg G, et al. WHO-EORTC classification for cutaneous lymphomas. Blood. 2005;105(10):3768–85. doi: 10.1182/blood-2004-09-3502.
  3. Korgavkar K, Xiong M, Weinstock М. Changing incidence trends of cutaneous T-cell lymphoma. JAMA Dermatol. 2013;149(11):1295–9. doi: 10.1001/jamadermatol.2013.5526.
  4. Imam MH, Shenoy PJ, Flowers CR, et al. Incidence and survival patterns of cutaneous T-cell lymphomas in the United States. Leuk Lymphoma. 2013;54(4):752–9. doi: 10.3109/10428194.2012.729831.
  5. Tan RH, Butterworth CM, McLaughlin H, et al. Mycosis fungoides—a disease of antigen persistence. Br J Dermatol. 1974;91(6):607–16. doi: 1111/j.1365-2133.1974.tb12449.x.
  6. Campbell JJ, Clark RA, Watanabe R, Kupper TS. Sezary syndrome and mycosis fungoides arise from distinct T-cell subsets: a biologic rationale for their distinct clinical behaviors. Blood. 2010;116(5):767–71. doi: 10.1182/blood-2009-11-251926.
  7. Berger CL, Hanlon D, Kanada D, et al. The growth of cutaneous T-cell lymphoma is stimulated by immature dendritic cells. 2002;99(8):2929–39. doi: 10.1182/blood.V99.8.2929.
  8. Wang L, Ni X, Covington K, et al. Genomic profiling of Sezary syndrome identifies alterations of key T cell signaling and differentiation genes. Nat Genet. 2015;47(12):1426–34. doi: 10.1038/ng.3444.
  9. Krejsgaard T, Willerslev-Olsen A, Lindahl LM, et al. Staphylococcal enterotoxins stimulate lymphoma-associated immune dysregulation. Blood. 2014;124(5):761–70. doi: 10.1182/blood-2014-01-551184.
  10. Gelfand JM, Shin DB, Neimann AL, et al. The risk of lymphoma in patients with psoriasis. J Invest Dermatol. 2006;126(10):2194–201. doi: 10.1038/sj.jid.5700410.
  11. Legendre L, Barnetche T, Mazereeuw-Hautier J, et al. Risk of lymphoma in patients with atopic dermatitis and the role of topical treatment: a systematic review and meta-analysis. J Am Acad Dermatol. 2015;72(6):992–1002. doi: 10.1016/j.jaad.2015.02.1116.
  12. Mirvish JJ, Pomerantz RG, Falo Jr LD, et al. Role of infectious agents in cutaneous T-cell lymphoma: facts and controversies. Clin Dermatol. 2013;31(4):423–31. doi: 10.1016/j.clindermatol.2013.01.009.
  13. Mirvish ED, Pomerantz RG, Geskin LJ. Infectious agents in cutaneous T-cell lymphoma. J Am Acad Dermatol. 2011;64(2):423–31. doi: 10.1016/j.jaad.2009.11.692.
  14. Белоусова И.Э., Самцов А.В. Федеральные клинические рекомендации по ведению больных лимфомами кожи. М., 2015. С. 13–25.
    [Belousova IE, Samtsov AV. Federalnye klinicheskie rekomendatsii po vedeniyu bolnykh limfomami kozhi. (Federal clinical guidelines for management of patients with cutaneous lymphomas.) Moscow; 2015. pp. 13–25. (In Russ)]
  15. Larocca C, Kupper T. Mycosis fungoides and sezary syndrome: an update. Hematol Oncol Clin. 2019;33(1):103–20. doi: 10.1016/j.hoc.2018.09.001.
  16. Agar NS, Wedgeworth E, Crichton S, et al. Survival outcomes and prognostic factors in mycosis fungoides/Sezary syndrome: validation of the revised International Society for Cutaneous Lymphomas/European Organisation for Research and Treatment of Cancer staging proposal. J Clin Oncol. 2010;28(31):4730–9. doi: 10.1200/jco.2009.27.7665.
  17. Sun G, Berthelot C, Li Y, Glass DA. Poor prognosis in non-Caucasian patients with early-onset mycosis fungoides. J Am Acad Dermatol. 2009;60(2):231–5. doi: 10.1016/j.jaad.2008.09.063.
  18. Talpur R, Singh L, Daulat S, et al. Long-term outcomes of 1,263 patients with mycosis fungoides and Sezary syndrome from 1982 to 2009. Clin Cancer Res. 2012;18(18):5051–60. doi: 10.1158/1078-0432.ccr-12-0604.
  19. Молочков А.В., Ковригина А.М., Кильдюшевский А.В., Караулов А.В. Лимфома кожи. М.: БИНОМ, 2012. 183 с.
    [Molochkov AV, Kovrigina AM, Kildyushevskii AV, Karaulov AV. Limfoma kozhi. (Cutaneous lymphoma.) Moscow: BINOM Publ.; 2012. 183 p. (In Russ)]
  20. Братцева Е.В., Ротанов С.В. Современные подходы к диагностике грибовидного микоза. Вестник дерматологии и венерологии. 2010;6:16–22.
    [Brattseva EV, Rotanov SV. Current approaches to the diagnosis of mycosis fungoides. Vestnik dermatologii i venerologii. 2010;6:16–22. (In Russ)]
  21. Guitart J, Kennedy J, Ronan S, et al. Histologic criteria for the diagnosis of mycosis fungoides: proposal for a grading system to standardize pathology reporting. J Cutan Pathol. 2001;28(4):174–83. doi: 10.1034/j.1600-0560.2001.028004174.x.
  22. Goteri G, Filosa A, Mannello B, et al. Density of neoplastic lymphoid infiltrate, CD8+ T cells, and CD1a+ dendritic cells in mycosis fungoides. J Clin Pathol. 2003;56(6):453–8. doi: 10.1136/jcp.56.6.453.
  23. Willemze R, Cerroni L, Kempf W, et al. The 2018 update of the WHO-EORTC classification for primary cutaneous lymphomas. Blood. 2019:133(16):1703–14. doi: 10.1182/blood.2019002852.
  24. Белоусова И.Э., Казаков Д.В., Криволапов Ю.А. Современные подходы к диагностике и лечению первичных лимфом кожи на основе новой ВОЗ-EORTC классификации. Т-клеточные лимфомы кожи. Архив патологии. 2007;69(5):11–7.
    [Belousova IE, Kazakov DV, Krivolapov YuA. Current approaches to the diagnosis and treatment of primary cutaneous lymphomas based on the new WHO-EORTC classification. Cutaneous T-cell lymphomas. Arkhiv patologii. 2007;69(5):11–7. (In Russ)]
  25. Поддубная И.В., Птушкин В.В., Белоусова И.Э. и др. Новые возможности системной терапии CD30+ первичных кожных Т-клеточных лимфом: резолюция. Современная онкология. 2020;22(2):79–81.
    [Poddubnaya IV, Ptushkin VV, Belousova IE, et al. New prospects for systemic treatment of primary cutaneous CD30+ T-cell lymphomas: resolution. Sovremennaya onkologiya. 2020;22(2):79–81. (In Russ)]
  26. Clark RA, Chong B, Mirchandani N, et al. The vast majority of CLA+ T cells are resident in normal skin. J Immunol. 2006;176(7):4431–9. doi: 10.4049/jimmunol.176.7.4431.
  27. Clark RA. Skin-resident T cells: the ups and downs of on site immunity. J Invest Dermatol. 2010;130(2):362–70. doi: 10.1038/jid.2009.247.
  28. Clark RA. Resident memory T cells in human health and disease. Sci Transl Med. 2015;7(269):269rv1. doi: 10.1126/scitranslmed.3010641.
  29. Watanabe R, Gehad A, Yang C, et al. Human skin is protected by four functionally and phenotypically discrete populations of resident and recirculating memory T cells. Sci Transl Med. 2015;7(279):279ra39. doi: 10.1126/scitranslmed.3010302.
  30. Golubovskaya V, Wu L. Different subsets of T cells, memory, effector functions, and CAR-T immunotherapy. Cancers. 2016;8(3):36. doi: 10.3390/cancers8030036.
  31. Sallusto F, Geginat J, Lanzavecchia A. Central memory and effector memory T cell subsets: function, generation, and maintenance. Annu Rev Immunol. 2004;22:745–63. doi: 10.1146/annurev.immunol.22.012703.104702.
  32. Butcher EC, Picker LJ. Lymphocyte homing and homeostasis. Science. 1996;272(5258):60–7. doi: 10.1126/science.272.5260.
  33. Wherry EJ, Teichgraber V, Becker TC, et al. Lineage relationship and protective immunity of memory CD8 T cell subsets. Nat Immunol. 2003;4(3):225–34. doi: 10.1038/ni889.
  34. Ma CS, Deenick EK, Batten M, Tangye SG. The origins, function, and regulation of T follicular helper cells. J Exp Med. 2012;209(7):1241–53. doi: 10.1084/jem.20120994.
  35. Deenick EK, Cindy SM, Brink R, et al. Regulation of T follicular helper cell formation and function by antigen presenting cells. Curr Opin Immunol. 2011;23(1):111–8. doi: 10.1016/j.coi.2010.10.007.
  36. Zhu J, Yamane H, Paul WE. Differentiation of effector CD4 T cell populations. Annu Rev Immunol. 2009;28:445–89. doi: 10.1146/annurev-immunol-030409-101212.
  37. Finotto S, Neurath MF, Glickman JN, et al. Development of spontaneous airway changes consistent with human asthma in mice lacking T-bet. Science. 2002;295(5553):336–8. doi: 10.1126/science.1065544.
  38. Bettelli E, Sullivan B, Szabo SJ, et al. Loss of T-bet, but not STAT1, prevents the development of experimental autoimmune encephalomyelitis. J Exp Med. 2004;200(1):79–87. doi: 10.1084/jem.20031819.
  39. Vowels BR, Lessin SR, Cassin M, et al. Th2 cytokine mRNA expression in skin in cutaneous T-cell lymphoma. J Invest Dermatol. 1994;103(5):669–73. doi: 10.1111/1523-1747.ep12398454.
  40. Miyagaki T, Sugaya M. Immunological milieu in mycosis fungoides and Sezary syndrome. J Dermatol. 2014;41(1):11–8. doi: 10.1111/1346-8138.12305.
  41. Hsi AC, Lee SJ, Rosman IS, et al. Expression of helper T cell master regulators in inflammatory dermatoses and primary cutaneous T-cell lymphomas: diagnostic implications. J Am Acad Dermatol. 2015;72(1):159–67. doi: 10.1016/j.jaad.2014.09.022.
  42. Sugaya M, Tokura Y, Hamada T, et al. Phase II study of iv interferon‐gamma in Japanese patients with mycosis fungoides. J Dermatol. 2014;41(1):50–6. doi: 10.1111/1346-8138.12341.
  43. Gu X, Wang Y, Zhang G, Li W, Tu P. Aberrant expression of BCL11B in mycosis fungoides and its potential role in interferon‐induced apoptosis. J Dermatol. 2013;40(8):596–605. doi: 10.1111/1346-8138.12160.
  44. Kataoka Y. Thymus and activation‐regulated chemokine as a clinical biomarker in atopic dermatitis. J Dermatol. 2014;41(3):221–9. doi: 10.1111/1346-8138.12440.
  45. Sugaya M, Morimura S, Suga H, Kawaguchi M. CCR 4 is expressed on infiltrating cells in lesional skin of early mycosis fungoides and atopic dermatitis. J Dermatol. 2015;42(6):613–5. doi: 10.1111/1346-8138.12852.
  46. Breitfeld D, Ohl L, Kremmer E, et al. Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. J Exp Med. 2000;192(11):1545–52. doi: 10.1084/jem.192.11.1545.
  47. Hardtke S, Ohl L, Forster R. Balanced expression of CXCR5 and CCR7 on follicular T helper cells determines their transient positioning to lymph node follicles and is essential for efficient B-cell help. Blood. 2005;106(6):1924–31. doi: 10.1182/blood-2004-11-4494.
  48. Krejsgaard T, Odum N, Geisler C, et al. Regulatory T cells and immunodeficiency in mycosis fungoides and Sezary syndrome. Leukemia. 2012;26(3):424–32. doi: 10.1038/leu.2011.237.
  49. Vonderheid EC, Pavlov I, Delgado JC, et al. Prognostic factors and risk stratification in early mycosis fungoides. Leuk Lymphoma. 2014;55(1):44–50. doi: 10.3109/10428194.2013.790541.
  50. Ungewickell A, Bhaduri A, Rios E, et al. Genomic analysis of mycosis fungoides and Sezary syndrome identifies recurrent alterations in TNFR2. Nat Genet. 2015;47(9):1056–60. doi: 10.1038/ng.3370.
  51. Zou W, Wolchok JD, Chen L. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations. Sci Transl Med. 2016;8(328):328rv4. doi: 10.1126/scitranslmed.aad7118.
  52. Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell. 2015;27(4):450–61. doi: 10.1016/j.ccell.2015.03.001.
  53. Cetinozman F, Jansen PM, Vermeer MH, Willemze R. Differential expression of programmed death-1 (PD-1) in Sezary syndrome and mycosis fungoides. Arch Dermatol. 2012;148(12):1379–85. doi: 10.1001/archdermatol.2012.2089.
  54. Kantekure K, Yang Y, Raghunath P, et al. Expression patterns of the immunosuppressive proteins PD-1/CD279 and PD-L1/CD274 at different stages of cutaneous T-cell lymphoma (CTCL)/mycosis fungoides (MF). Am J Dermatopathol. 2012;34(1):126. doi: 10.1097/dad.0b013e31821c35cb.
  55. Togashi Y, Shitara K, Nishikawa H. Regulatory T cells in cancer immunosuppression—implications for anticancer therapy. Nat Rev Clin Oncol. 2019;16(6):356–71. doi: 10.1038/s41571-019-0175-7.
  56. Clark RA. Regulation gone wrong: a subset of Sezary patients have malignant regulatory T cells. J Invest Dermatol. 2009;129(12):2747–50. doi: 10.1038/jid.2009.290.
  57. Gholami MD, Kardar GA, Saeedi Y, et al. Exhaustion of T lymphocytes in the tumor microenvironment: significance and effective mechanisms. Cell Immunol. 2017;322:1–14. doi: 10.1016/j.cellimm.2017.10.002.
  58. Murray D, McMurray JL, Eldershaw S, et al. Progression of mycosis fungoides occurs through divergence of tumor immunophenotype by differential expression of HLA-DR. Blood Adv. 2019:3(4):519–30. doi: 10.1182/bloodadvances.2018025114.
  59. Vermeer MH, van Doorn R, Dukers D, et al. CD8+ T cells in cutaneous T-cell lymphoma: expression of cytotoxic proteins, Fas ligand, and killing inhibitory receptors and their relationship with clinical behavior. J Clin Oncol. 2001;19(23):4322–9. doi: 10.1200/jco.2001.19.23.4322.
  60. Goteri G, Filosa A, Mannello B, et al. Density of neoplastic lymphoid infiltrate, CD8+ T cells, and CD1a+ dendritic cells in mycosis fungoides. J Clin Pathol. 2003;56(6):453–8. doi: 10.1136/jcp.56.6.453.
  61. Hoppe RT, Medeiros LJ, Warnke RA, Wood GS. CD8-positive tumor-infiltrating lymphocytes influence the long-term survival of patients with mycosis fungoides. J Am Acad Dermatol. 1995;32(3):448–53. doi: 10.1016/0190-9622(95)90067-5.
  62. Gjerdrum LM, Woetmann A, Odum N, et al. FOXP3+ regulatory T cells in cutaneous T-cell lymphomas: association with disease stage and survival. Leukemia. 2007;21(12):2512–8. doi: 10.1038/sj.leu.2404913.
  63. Berger CL, Hanlon D, Kanada D, et al. The growth of cutaneous T-cell lymphoma is stimulated by immature dendritic cells. Blood. 2002;99(8):2929–39. doi: 10.1182/blood.v99.8.2929.
  64. Wong HK, Wilson AJ, Gibson HM, et al. Increased expression of CTLA-4 in malignant T cells from patients with mycosis fungoides–cutaneous T-cell lymphoma. J Invest Dermatol. 2006;126(1):212–9. doi: 10.1038/sj.jid.5700029.
  65. Querfeld C, Curran SA, Leung S, et al. T cells in CTCL have an exhausted phenotype while cutaneous dendritic cells display a normally activated mature phenotype. Blood. 2014;124(21):1695. doi: 10.1182/blood.v124.21.1695.1695.
  66. Sugaya M, Miyagaki T, Ohmatsu H, et al. Association of the numbers of CD163+ cells in lesional skin and serum levels of soluble CD163 with disease progression of cutaneous T cell lymphoma. J Dermatol Sci. 2012;68(1):45–51. doi: 10.1016/j.jdermsci.2012.07.007.
  67. Wu X, Schulte BC, Zhou Y, et al. Depletion of M2-like tumor-associated macrophages delays cutaneous T-cell lymphoma development in vivo. J Invest Dermatol. 2014;134(11):2814–22. doi: 10.1038/jid.2014.206.
  68. Jullie ML, Carlotti M, Vivot A Jr, et al. CD20 antigen may be expressed by reactive or lymphomatous cells of transformed mycosis fungoides: diagnostic and prognostic impact Am J Surg Pathol. 2013;37(12):1845–54. doi: 10.1097/pas.0000000000000091.
  69. Nelson BH. CD20+ B cells: the other tumor-infiltrating lymphocytes. J Immunol. 2010;185(9):4977–82. doi: 10.4049/jimmunol.1001323.
  70. Theurich S, Schlaak M, Steguweit H, et al. Targeting tumor-infiltrating B cells in cutaneous T-cell lymphoma. J Clin Oncol. 2016;34(12):e110–e116. doi: 10.1200/jco.2013.50.9471.
  71. Choi J, Goh G, Walradt T, et al. Genomic landscape of cutaneous T cell lymphoma. Nat Genet. 2015;47(9):1011–9. doi: 10.1038/ng.3356.
  72. Park J, Yang J, Wenzel AT, et al. Genomic analysis of 220 CTCLs identifies a novel recurrent gain-of-function alteration in RLTPR (p. Q575E). Blood. 2017;130(12):1430–40. doi: 10.1182/blood-2017-02-768234.
  73. Gonzalez BR, Zain J, Rosen ST, Querfeld C. Tumor microenvironment in mycosis fungoides and Sezary syndrome. Curr Opin Oncol. 2016;28(1):88–96. doi: 10.1097/CCO.0000000000000243
  74. Axelrod PI, Lorber B, Vonderheid EC. Infections complicating mycosis fungoides and Sezary syndrome. 1992;267(10):1354–8. doi: 10.1001/jama.267.10.1354.
  75. Netchiporouk E, Litvinov IV, Moreau L, et al. Deregulation in STAT signaling is important for cutaneous T-cell lymphoma (CTCL) pathogenesis and cancer progression. Cell Cycle. 2014;13(21):3331–5. doi: 10.4161/15384101.2014.965061.
  76. Kirsch IR, Watanabe R, O’Malley JT, et al. TCR sequencing facilitates diagnosis and identifies mature T cells as the cell of origin in CTCL. Science Transl Med. 2015;7(308):308ra158. doi: 10.1126/scitranslmed.aaa9122.
  77. Российские клинические рекомендации по диагностике и лечению лимфопролиферативных заболеваний. Под ред. И.В. Поддубной, В.Г. Савченко. М.: Буки Веди, 2016. С. 85–91.
    [Poddubnaya IV, Savchenko VG, eds. Rossiiskie klinicheskie rekomendatsii po diagnostike i lecheniyu limfoproliferativnykh zabolevanii. (Russian clinical guidelines on diagnosis and treatment of lymphoproliferative disorders.) Moscow: Buki Vedi Publ.; 2016. 85–91. (In Russ)]
  78. Сидорова Ю.В. Т-клеточная клональность в диагностике лимфопролиферативных заболеваний: Дис.… канд. мед. наук. М., 2004.
    [Sidorova YuV. T-kletochnaya klonalnost v diagnostike limfoproliferativnykh zabolevanii. (T-cell clonality in the diagnosis of lymphoproliferative) [dissertation] Moscow; 2004. (In Russ)]
  79. Olsen E, Vonderheid E, Pimpinelli N, et al. Revisions to the staging and classification of mycosis fungoides and Sezary syndrome: a proposal of the International Society for Cutaneous Lymphomas (ISCL) and the cutaneous lymphoma task force of the European Organization of Research and Treatment of Cancer (EORTC). Blood. 2007;110(6):1713–22. doi: 10.1182/blood-2008-02-142653.
  80. Scarisbrick JJ, Prince HM, Vermeer MH, et al. Cutaneous Lymphoma International Consortium study of outcome in advanced stages of mycosis fungoides and Sezary syndrome: effect of specific prognostic markers on survival and development of a prognostic model. J Clin Oncol. 2015;33(32):3766. doi: 10.1200/JCO.2015.61.7142.
  81. de Masson A, O’Malley JT, Elco CP, et al. High-throughput sequencing of the T cell receptor β gene identifies aggressive early-stage mycosis fungoides. Sci Transl Med. 2018;10(440):eaar5894. doi: 10.1126/scitranslmed.aar5894.
  82. Trautinger F, Eder J, Assaf C, et al. European Organisation for Research and Treatment of Cancer consensus recommendations for the treatment of mycosis fungoides/Sezary syndrome–Update 2017. Eur J Cancer. 2017;77:57–74. doi: 10.1016/j.ejca.2017.02.027.
  83. Олисова О.Ю., Сыдиков А.А., Чупров И.Н. и др. Эритродермическая форма грибовидного микоза: алгоритм диагностики и лечения. Клиническая онкогематология. 2018;11(4):295–302. doi: 10.21320/2500-2139-2018-11-4-295-302.
    [Olisova OYu, Sydikov AA, Chuprov IN, et al. Erythrodermic Mycosis Fungoides: The Algorithm of Diagnosis and Treatment. Clinical oncohematology. 2018;11(4):295–302. doi: 10.21320/2500-2139-2018-11-4-295-302. (In Russ)]
  84. Zinzani PL, Venturini F, Stefoni V, et al. Gemcitabine as single agent in pretreated T-cell lymphoma patients: evaluation of the long-term outcome. Ann Oncol. 2010;21(4):860–3. doi: 10.1093/annonc/mdp508.
  85. Hanel W, Briski R, Ross CW, et al. A retrospective comparative outcome analysis following systemic therapy in mycosis fungoides and Sezary syndrome. Am J Hematol. 2016;91(12):E491–E495. doi: 10.1002/ajh.24564.
  86. Damsky WE, Choi J. Genetics of cutaneous T cell lymphoma: from bench to bedside. Curr Treat Options Oncol. 2016;17(7):1–14. doi: 10.1007/s11864-016-0410-8.
  87. Weng WK, Armstrong R, Arai S, et al. Non-myeloablative allogeneic transplantation resulting in clinical and molecular remission with low Non-Relapse Mortality (NRM) in patients with advanced stage Mycosis Fungoides (MF) and Sezary Syndrome (SS). Blood. 2014;124(21):2544. doi: 10.1182/blood.v124.21.2544.2544.