New diagnostic biomarkers for early stages of cutaneous T-cell lymphoma

封面

如何引用文章

全文:

开放存取 开放存取
受限制的访问 ##reader.subscriptionAccessGranted##
受限制的访问 订阅或者付费存取

详细

Currently, the diagnosis of early stages of cutaneous T-cell lymphomas (CTCL) is one of the most challenging tasks in dermatology. This review is devoted to the analysis of new immunohistochemical (IHC) markers that could be considered diagnostic for the detection of CTCL, as well as potential targets for targeted therapy of the disease.

The aim of this review was to determine and summarize new promising biomarkers that are not currently used for the diagnosis of early stages of CTCL.

Material and methods: the analysis and systematization of scientific literature over the past 5 years was carried out in the PubMed database using the search algorithm: “cutaneous T-cell lymphoma” AND (“immunohistochem” OR “IHC” OR “expression”).

Results. All found biomarkers were divided into 3 groups:

  • Tumor progression markers: OX40 и OX40L, ICOS, TOX, GATA-3, TSP-1, CD47, YKL-40, IKZF2, E-FABP, CXCR4, CD69, HSPA1A, ZFP36, TXNIP and IL7R;
  • Differential diagnostic markers: STAT4, YKL-40, BCL11B, CD70, hBD-2 and psoriasin;
  • Tumor microenvironment markers: IL-10, PD-L1, FAP-α, CD69, granzyme B, NKp46, TIM3, CD57 and LAG3.

Conclusion. The most promising marker to diagnose the early stages is YKL-40 since it can serve as both a prognostic and differential diagnostic marker.

全文:

受限制的访问

作者简介

Olga Gafurova

Federal State Autonomous Educational Institution of Higher Education I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

编辑信件的主要联系方式.
Email: lobanova_o_a@staff.sechenov.ru
ORCID iD: 0000-0002-6813-3374

Pathologist, Assistant of the Institute of Clinical Morphology and Digital Pathology

俄罗斯联邦, st. Trubetskaya, 8/2, Moscow, 119048

Oleg Danilik

Federal State Autonomous Educational Institution of Higher Education I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Email: oleg.danilik7@gmail.com
ORCID iD: 0009-0001-8841-6275

student of the Institute of Biodesign and Modelling of Complex Systems

俄罗斯联邦, st. Trubetskaya, 8/2, Moscow, 119048

Olesya Anufrieva

Federal State Autonomous Educational Institution of Higher Education I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Email: benrimasalmin@bk.ru
ORCID iD: 0009-0002-2525-5272

student of the Institute of Pharmacy named after A.P. Nelubin

俄罗斯联邦, st. Trubetskaya, 8/2, Moscow, 119048

Yana Syrovatskaya

Federal State Autonomous Educational Institution of Higher Education I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Email: yana.syr@bk.ru
ORCID iD: 0009-0004-7095-3955

student of the Institute of Pharmacy named after A.P. Nelyubin

俄罗斯联邦, st. Trubetskaya, 8/2, Moscow, 119048

Margarita Orobets

Federal State Autonomous Educational Institution of Higher Education I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Email: margaret.orobets@gmail.com
ORCID iD: 0009-0002-4231-5329

student of the Institute of Pharmacy named after A.P. Nelyubin

俄罗斯联邦, st. Trubetskaya, 8/2, Moscow, 119048

Regina Artykova

Federal State Autonomous Educational Institution of Higher Education I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Email: Artykovara@gmail.com
ORCID iD: 0009-0000-4949-7183

student of the Institute of Clinical Medicine named after N.V. Sklifosovsky

俄罗斯联邦, st. Trubetskaya, 8/2, Moscow, 119048

Eva Gosteeva

Federal State Autonomous Educational Institution of Higher Education I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Email: gosteeva_e_a@student.sechenov.ru
ORCID iD: 0009-0001-1541-4439

student of the N.F. Filatov Clinical Institute of Pediatric Health

俄罗斯联邦, st. Trubetskaya, 8/2, Moscow, 119048

Ekaterina Rudenko

Federal State Autonomous Educational Institution of Higher Education I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Email: rudenko_e_e@staff.sechenov.ru
ORCID iD: 0000-0002-0000-1439

Candidate of Medical Sciences, Deputy Director for Research, Professor Assistant at the Institute of Clinical Morphology and Digital Pathology

俄罗斯联邦, st. Trubetskaya, 8/2, Moscow, 119048

Vera Smolyannikova

Federal State Autonomous Educational Institution of Higher Education I.M.Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)

Email: smva@bk.ru
ORCID iD: 0000-0002-7759-5378

Doctor of Medical Sciences, Professor of the Institute of Clinical Morphology and Digital Pathology

俄罗斯联邦, st. Trubetskaya, 8/2, Moscow, 119048

参考

  1. Dobos G., Miladi M., Michel L., Ram-Wolff C., Battistella M., Bagot M. et al. Recent advances on cutaneous lymphoma epidemiology. La Presse Médicale. 2022; 51 (1): 104108. https://doi.org/10.1016/j.lpm.2022.104108
  2. Демина О.М., Акилов О.Е., Румянцев А.Г. Т-клеточные лимфомы кожи: современные данные патогенеза, клиники и терапии. Онкогематология. 2018; 13 (3): 25–38. https://doi.org/10.17650/1818-8346-2018-13-3-25-38. [Demina O.M., Akilov O.E., Rumyantsev A.G. Cutaneous T-cell lymphomas: modern data of pathogenesis, clinics and therapy. Onkogematologiâ. 2018; 13 (3): 25–38 (in Russian)]
  3. Kawai H., Ando K., Maruyama D., Yamamoto K., Kiyohara E., Terui Y., Fukuhara N. et al. Phase II study of E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma. Cancer Science. 2021; 112 (6): 2426–35. https://doi.org/10.1111/cas.14906
  4. Поддубная И.В., Савченко В.В. Российские клинические рекомендации по диагностике и лечению лимфопролиферативных заболеваний. ООО Буки Веди, 2016. [Poddubnaya I.V., Savchenko V.V. Rossijskie klinicheskie rekomendacii po diagnostike i lecheniyu limfoproliferativnyh zabolevanij. OOO Buki Vedi, 2016 (in Russian)]
  5. Geller S., Hollmann T.J., Horwitz S.M., Myskowski P.L., Pulitzer M. C-C chemokine receptor 4 expression in CD8+ cutaneous T-cell lymphomas and lymphoproliferative disorders, and its implications for diagnosis and treatment. Histopathology. 2020; 76 (2): 222–32. https://doi.org/10.1111/his.13960
  6. Olisova O.Y., Grekova E.V., Varshavsky V.A., Gorenkova L.G., Alekseeva E.A., Zaletaev D.V., Sydikov A.A. Current possibilities of the differential diagnosis of plaque parapsoriasis and the early stages of mycosis fungoides. Arkh Patol. 2019; 81 (1): 9–17. https://doi.org/10.17116/patol2019810119
  7. Xu B., Liu F., Gao Y., Sun J., Li Y., Lin Y., Liu X. et al. High Expression of IKZF2 in Malignant T Cells Promotes Disease Progression in Cutaneous T Cell Lymphoma. Acta Derm Venereol. 2021; 101 (12): adv00613. https://doi.org/10.2340%2Factadv.v101.570
  8. Yang C., Mai H., Peng J., Zhou B., Hou J., Jiang D. STAT4: an immunoregulator contributing to diverse human diseases. Int. J. Biol. Sci. 2020; 16 (9): 1575–85. https://doi.org/10.7150%2Fijbs.41852
  9. Sun S., Dong H., Yan T., Li J., Liu B., Shao P., Li J., Liang C. Role of TSP-1 as prognostic marker in various cancers: a systematic review and meta-analysis. BMC Med Genet. 2020; 21 (1): 139. https://doi.org/10.1186/s12881-020-01073-3
  10. Tizaoui K., Yang J.W., Lee K.H., Kim J.H., Kim M., Yoon S., Jung Y. et al. The role of YKL-40 in the pathogenesis of autoimmune diseases: a comprehensive review. Int. J. Biol. Sci. 2022; 18 (9): 3731–46. https://doi.org/10.7150/ijbs.67587
  11. Chang M.C., Chiang P.F., Kuo Y.J., Peng C.L., Chen I.C., Huang C.Y., Chen C.A., Chiang Y.C. Develop companion radiopharmaceutical YKL40 antibodies as potential theranostic agents for epithelial ovarian cancer. Biomed Pharmacother. 2022; 155: 113668. https://doi.org/10.7150%2Fjca.62285
  12. Andtbacka R.H.I., Wang Y., Pierce R.H., Campbell J.S., Yushak M., Milhem M., Ross M. еt al. Mavorixafor, an Orally Bioavailable CXCR4 Antagonist, Increases Immune Cell Infiltration and Inflammatory Status of Tumor Microenvironment in Patients with Melanoma. Cancer Res Commun. 2022; 2 (8): 904–13. https://doi.org/10.1158/2767-9764.crc-22-0090
  13. Zhang Y., Luo Y., Qin S.L., Mu Y.F., Qi Y., Yu M.H., Zhong M. The clinical impact of ICOS signal in colorectal cancer patients. Oncoimmunology. 2016; 5 (5): e1141857. https://doi.org/10.1080/2162402x.2016.1141857
  14. Xu-Monette Z.Y., Zhou J., Young K.H. PD-1 expression and clinical PD-1 blockade in B-cell lymphomas. Blood. 2018; 131 (1): 68–83. https://doi.org/10.1182/blood-2017-07-740993
  15. Wang L., Rocas D., Dalle S., Sako N., Pelletier L., Martin N., Dupuy A. еt al. Primary cutaneous peripheral T-cell lymphomas with a T-follicular helper phenotype: an integrative clinical, pathological and molecular case series study. Br. J. Dermatol. 2022; 187 (6): 970–80. https://doi.org/10.1111/bjd.21791
  16. Karpathiou G., Papoudou-Bai A., Ferrand E., Dumollard J.M., Peoc’h M. STAT6: A review of a signaling pathway implicated in various diseases with a special emphasis in its usefulness in pathology. Pathol Res Pract. 2021; 223: 153477. https://doi.org/10.1016/j.prp.2021.153477
  17. Zhang Y., Zhang Y., Gu W., Sun B. TH1/TH2 cell differentiation and molecular signals. Adv Exp. Med. Biol. 2014; 841: 15–44. https://doi.org/10.1007/978-94-017-9487-9_2
  18. Murga-Zamalloa C., Wilcox R.A. GATA-3 in T-cell lymphoproliferative disorders. IUBMB Life. 2020; 72 (1): 170–7. https://doi.org/10.1002%2Fiub.2130
  19. Tindemans I., Serafini N., Di Santo J.P., Hendriks R.W. GATA-3 function in innate and adaptive immunity. Immunity. 2014; 41 (2): 191–206. https://doi.org/10.1016/j.immuni.2014.06.006
  20. Hetemäki I., Kaustio M., Kinnunen M., Heikkilä N., Keskitalo S., Nowlan K., Miettinen S. et al. Loss-of-function mutation in IKZF2 leads to immunodeficiency with dysregulated germinal center reactions and reduction of MAIT cells. Sci Immunol. 2021; 6 (65): eabe3454. https://doi.org/10.1126/sciimmunol.abe3454
  21. Ouyang W., O’Garra A. IL-10 Family Cytokines IL-10 and IL-22: from Basic Science to Clinical Translation. Immunity. 2019; 50 (4): 871–91. https://doi.org/10.1016/j.immuni.2019.03.020
  22. Hayat S.M.G., Bianconi V., Pirro M., Jaafari M.R., Hatamipour M., Sahebkar A. CD47: role in the immune system and application to cancer therapy. Cell Oncol (Dordr). 2020; 43 (1): 19–30. https://doi.org/10.1007/s13402-019-00469-5
  23. Chakraborty S., Kubatzky K.F., Mitra D.K. An Update on Interleukin-9: From Its Cellular Source and Signal Transduction to Its Role in Immunopathogenesis. Int. J. Mol. Sci. 2019; 20 (9): 2113. https://doi.org/10.3390/ijms20092113
  24. Matusiewicz K., Iwańczak B., Matusiewicz M. Th9 lymphocytes and functions of interleukin 9 with the focus on IBD pathology. Adv Med. Sci. 2018; 63 (2): 278–84. https://doi.org/10.1016/j.advms.2018.03.002
  25. Cibrián D., Sánchez-Madrid F. CD69: from activation marker to metabolic gatekeeper. Eur. J. Immunol. 2017; 47 (6): 946–53. https://doi.org/10.1002/eji.201646837
  26. Gorabi A.M., Hajighasemi S., Kiaie N., Gheibi Hayat S.M., Jamialahmadi T., Johnston T.P., Sahebkar A. The pivotal role of CD69 in autoimmunity. J. Autoimmun. 2020; 111: 102453. https://doi.org/10.1016/j.jaut.2020.102453
  27. Moar P., Tandon R. Galectin-9 as a biomarker of disease severity. Cell Immunol. 2021; 361: 104287. https://doi.org/10.1016/j.cellimm.2021.104287
  28. Suzuki H., Boki H., Kamijo H., Nakajima R., Oka T., Shishido-Takahashi N. et al. YKL-40 Promotes Proliferation of Cutaneous T-Cell Lymphoma Tumor Cells through Extracellular Signal-Regulated Kinase Pathways. J. Invest Dermatol. 2020; 140 (4): 860–868.e3. https://doi.org/10.1016/j.jid.2019.09.007
  29. Kawana Y., Suga H., Kamijo H., Miyagaki T., Sugaya M., Sato S. Roles of OX40 and OX40 Ligand in Mycosis Fungoides and Sézary Syndrome. Int. J. Mol. Sci. 2021; 22 (22): 12576. https://doi.org/10.3390/ijms222212576
  30. Di Raimondo C., Rubio-Gonzalez B., Palmer J., Weisenburger D.D., Zain J., Wu X., Han Z. et al. Expression of immune checkpoint molecules programmed death protein 1, programmed death-ligand 1 and inducible T-cell co-stimulator in mycosis fungoides and Sézary syndrome: association with disease stage and clinical outcome. Br. J. Dermatol. 2022; 187 (2): 234–43. https://doi.org/10.1111/bjd.21063
  31. Atwa H.A., Abdelrahman D.I. The Value of Immunohistochemical Expression of TOX, ICOS, and GATA-3 in the Diagnosis of Mycosis Fungoides. Appl Immunohistochem Mol Morphol. 2023; 31 (3): 163–71. https://doi.org/10.1097/pai.0000000000001110
  32. Kamijo H., Miyagaki T., Takahashi-Shishido N., Nakajima R., Oka T., Suga H., Sugaya M., Sato S. Thrombospondin-1 promotes tumor progression in cutaneous T-cell lymphoma via CD47. Leukemia. 2020; 34 (3): 845–56. https://doi.org/10.1038/s41375-019-0622-6
  33. Takahashi-Shishido N., Sugaya M., Morimura S., Suga H., Oka T., Kamijo H., Miyagaki T., Sato S. Mycosis fungoides and Sézary syndrome tumor cells express epidermal fatty acid-binding protein, whose expression decreases with loss of epidermotropism. J. Dermatol. 2021; 48 (5): 685–9. https://doi.org/10.1111/1346-8138.15775
  34. Rindler K., Jonak C., Alkon N., Thaler F.M., Kurz H., Shaw L.E., Stingl G. et al. Single-cell RNA sequencing reveals markers of disease progression in primary cutaneous T-cell lymphoma. Mol Cancer. 2021; 20 (1): 124. https://doi.org/10.1186/s12943-021-01419-2
  35. Liu J., Zheng X., Pang X., Li L., Wang J., Yang C., Du G. Ganglioside GD3 synthase (GD3S), a novel cancer drug target. Acta Pharm Sin B. 2018; 8 (5): 713–20. https://doi.org/10.1016%2Fj.apsb.2018.07.009
  36. Lennon M.J., Jones S.P., Lovelace M.D., Guillemin G.J., Brew B.J. Bcl11b-A Critical Neurodevelopmental Transcription Factor-Roles in Health and Disease. Front Cell Neurosci. 2017; 11: 89. https://doi.org/10.3389%2Ffncel.2017.00089
  37. Wajant H. Therapeutic targeting of CD70 and CD27. Expert Opin Ther Targets. 2016; 20 (8): 959–73. https://doi.org/10.1517/14728222.2016.1158812
  38. Sans-de San Nicolàs L., Czarnowicki T., Akdis M., Pujol R.M., Lozano-Ojalvo D., Leung D.Y.M., Guttman-Yassky E., Santamaria-Babi L.F. CLA+ memory T cells in atopic dermatitis. Allergy. 2023. https://doi.org/10.1111/all.15816
  39. Cieślik M., Bagińska N., Górski A., Jończyk-Matysiak E. Human β-Defensin 2 and Its Postulated Role in Modulation of the Immune Response. Cells. 2021; 10 (11): 2991. https://doi.org/10.3390/cells10112991
  40. Pan M., Zhang F., Qu K., Liu C., Zhang J. TXNIP: A Double-Edged Sword in Disease and Therapeutic Outlook. Oxid Med Cell Longev. 2022; 2022: 7805115. https://doi.org/10.1155%2F2022%2F7805115
  41. Fang H., Khoury J.D., Torres-Cabala C.A., Ng S.B., Xu J., El Hussein S., Hu S. et al. Expression pattern and diagnostic utility of BCL11B in mature T- and NK-cell neoplasms. Pathology. 2022; 54 (7): 893–9. https://doi.org/10.1016/j.pathol.2022.04.012
  42. Wu C.H., Wang L., Yang C.Y., Wen K.W., Hinds B., Gill R., McCormick F. et al. Targeting CD70 in cutaneous T-cell lymphoma using an antibody-drug conjugate in patient-derived xenograft models. Blood Adv. 2022; 6 (7): 2290–302. https://doi.org/10.1182/bloodadvances.2021005714
  43. Wehkamp U., Jost M., Wehkamp K., Harder J. Dysregulated Expression of Antimicrobial Peptides in Skin Lesions of Patients with Cutaneous T-cell Lymphoma. Acta Derm Venereol. 2020; 100 (1): adv00017. https://doi.org/10.2340/00015555-3372
  44. Peru S., Prochazkova-Carlotti M., Cherrier F., Velazquez J., Richard E., Idrissi Y., Cappellen D. et al. Cutaneous Lymphocyte Antigen Is a Potential Therapeutic Target in Cutaneous T-Cell Lymphoma. J. Invest Dermatol. 2022; 142 (12): 3243–3252.e10. https://doi.org/10.1016/j.jid.2022.06.016
  45. Zheng Y., Fang Y.C., Li J. PD-L1 expression levels on tumor cells affect their immunosuppressive activity. Oncol Lett. 2019; 18 (5): 5399–407. https://doi.org/10.3892/ol.2019.10903
  46. Mori N., Jin J., Krishnamachary B., Mironchik Y., Wildes F., Vesuna F., Barnett J.D., Bhujwalla Z.M. Functional roles of FAP-α in metabolism, migration and invasion of human cancer cells. 2023. https://doi.org/10.3389/fonc.2023.1068405
  47. Mehdi S.J., Moerman-Herzog A., Wong H.K. Normal and cancer fibroblasts differentially regulate TWIST1, TOX and cytokine gene expression in cutaneous T-cell lymphoma. BMC Cancer. 2021; 21 (1): 492. https://doi.org/10.1186/s12885-021-08142-7
  48. Scheffschick A., Nenonen J., Xiang M., Winther A.H., Ehrström M., Wahren-Herlenius M. et al. Skin infiltrating NK cells in cutaneous T-cell lymphoma are increased in number and display phenotypic alterations partially driven by the tumor. Front Immunol. 2023; 14: 1168684. https://doi.org/10.3389/fimmu.2023.1168684
  49. Wu X., Hsu D.K., Wang K.H., Huang Y., Mendoza L., Zhou Y., Hwang S.T. IL-10 is overexpressed in human cutaneous T-cell lymphoma and is required for maximal tumor growth in a mouse model. Leuk Lymphoma. 2019; 60 (5): 1244–52. https://doi.org/10.1080/10428194.2018.1516037

补充文件

附件文件
动作
1. JATS XML
下载
2. Groups of new biomarkers for the diagnosis of cutaneous T-Cell lymphoma

下载 (140KB)
索引源数据

版权所有 © Russkiy Vrach Publishing House, 2025