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The cytokine milieu orchestrates the Th1/Th2/Th17 and Treg cells roles in acute lymphoblastic leukemia patients

Hunar Dhahir Ismael
Department of Clinical Analysis, College of Pharmacy, Hawler Medical University, Erbil, Kurdistan region, Iraq.
Soza Tharwat Baban
Department of Medical Microbiology, College of Health Sciences, Hawler Medical University, Erbil, Kurdistan region, Iraq.
Zahra Abdulqader Amin
Department of Pharmacognosy, College of Pharmacy, Hawler Medical University, Erbil, Iraq.
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Copyright (c) 2026 Hunar Dhahir Ismael , Soza Tharwat Baban, Zahra Abdulqader Amin (Author)

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Abstract

Background and objective: T cells perform a crucial role in mediating immune responses to a diversity of pathogens. Different types of T cells play a great role in immune response, including T helper cells 1 (Th1), T helper cells 2 (Th2), T helper cells 17 (Th17), and T regulatory cells (Treg cells). Each of these cells produces different types of cytokines, and irregularities of their levels have been linked to various malignancies.

Methods: In this case-control study, demographic information was collected from patients suffering from acute lymphoblastic leukemia (ALL), and then concentrations of C-reactive protein (CRP) and total white blood cell (WBC) count, beside interleukins 2,4,10,13,17 and 22(IL-2, IL-4 IL-10, IL-13, IL17, IL22), tumor necrosis factor alpha (TNF-α) and interferon gamma (INF-γ) cytokines were tested in their sera.

Results: Th-associated pro-inflammatory cytokines IFN-γ, IL-2, TNF-α, IL-4, IL-13, IL-17, and IL-22 were significantly decreased in ALL patients compared to healthy controls. On the other hand, immunosuppressive cytokine IL-10 associated with Treg cells was markedly elevated in the patient group. Elevated CRP and WBC levels were also observed in ALL patients, indicating systemic inflammation.

Conclusion: The cytokine profile in ALL patients is indicative of a shift to immunosuppressive status that could facilitate leukemic development. The reduction in pro-inflammatory cytokines and elevation of IL-10 levels point towards suppressed anti-tumor immunity. These findings highlight the significance of Th1/Th2/Th17/Treg cell interactions in ALL and suggest that manipulation of cytokine disbalance could yield new diagnostic or therapeutic avenues.

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References

  1. Juliusson G, Hough R. Leukemia. Prog Tumor Res. 2016;43:87-100. DOI: 10.1159/000447076
  2. Strati P, Shanafelt TD. Monoclonal B-cell lymphocytosis and early-stage chronic lymphocytic leukemia: diagnosis, natural history, and risk stratification. Blood. 2015;126(4):454-62. DOI: 10.1182/blood-2015-02-585059
  3. Luca DC. Update on Lymphoblastic Leukemia/Lymphoma. Clin Lab Med. 2021;41(3):405-16. DOI: 10.1016/j.cll.2021.04.003
  4. DeAngelo DJ, Jabbour E, Advani A. Recent Advances in Managing Acute Lymphoblastic Leukemia. Am Soc Clin Oncol Educ Book. 2020;40:330-42. DOI: 10.1200/EDBK_280175
  5. Wiggins M, Stevenson W. Genetic predisposition in acute leukaemia. Int J Lab Hematol. 2020;42 Suppl 1:75-81. DOI: 10.1111/ijlh.13173
  6. Annunziato F, Cosmi L, Liotta F, Maggi E, Romagnani S. Human Th1 dichotomy: origin, phenotype and biologic activities. Immunology. 2014;144(3):343-51. DOI: 10.1111/imm.12399
  7. Zhang XL, Komada Y, Chipeta J, Li QS, Inaba H, Azuma E, et al. Intracellular cytokine profile of T cells from children with acute lymphoblastic leukemia. Cancer Immunol Immunother. 2000;49(3):165-72. DOI: 10.1007/s002620050616
  8. Yin HQ, Qiao ZH, Zhu L, Zhang L, Su LP, Lu YJ. [Levels of intracellular IL-6 and IFN-gamma in children with acute lymphoblastic leukemia]. Zhongguo Dang Dai Er Ke Za Zhi. 2006;8(6):461-3. PMID: 17178034
  9. Schober S, Rottenberger JM, Hilz J, Schmid E, Ebinger M, Feuchtinger T, et al. Th1 cytokines in pediatric acute lymphoblastic leukemia. Cancer Immunol Immunother. 2023;72(11):3621-34. DOI: 10.1007/s00262-023-03512-5
  10. Cao Q, Zheng R, He R, Wang T, Xu M, Lu J, et al. Age-specific prevalence, subtypes and risk factors of metabolic diseases in Chinese adults and the different patterns from other racial/ethnic populations. BMC Public Health. 2022;22(1):2078. DOI: 10.1186/s12889-022-14555-1
  11. Hacker K. The Burden of Chronic Disease. Mayo Clin Proc Innov Qual Outcomes. 2024;8(1):112-9. DOI: 10.1016/j.mayocpiqo.2023.08.005
  12. Park SE, Ko S-H, Kim JY, Kim K, Moon JH, Kim NH, et al. Diabetes Fact Sheets in Korea 2024. Diabetes Metab J. 2025;49(1):24-33. DOI: 10.4093/dmj.2024.0818
  13. Vaingankar JA, Abdin E, Chong SA, Shafie S, Sambasivam R, Zhang YJ, et al. The association of mental disorders with perceived social support, and the role of marital status: results from a national cross-sectional survey. Arch Public Health. 2020;78(1):108. DOI: 10.1186/s13690-020-00476-1
  14. Adelman AS, McLaughlin CC, Wu XC, Chen VW, Groves FD. Urbanisation and incidence of acute lymphocytic leukaemia among United States children aged 0-4. Br J Cancer. 2005;92(11):2084-8. DOI: 10.1038/sj.bjc.6602607
  15. Organization WH. Global Health Observatory data repository. 2025
  16. Amiri S. Unemployment associated with major depression disorder and depressive symptoms: a systematic review and meta-analysis. Int J Occup Saf Ergon. 2022;28(4):2080-92. DOI: 10.1080/10803548.2021.1954793
  17. Chen T-Y, Geng J-H, Chen S-C, Lee J-I. Living alone is associated with a higher prevalence of psychiatric morbidity in a population-based cross-sectional study. Front Public Health. 2022;10:1054615. DOI: 10.3389/fpubh.2022.1054615
  18. (OECD) OfEC-oaD. Health. accessed 2025.
  19. Sharif L, Alasmee N. Barriers and Facilitators to Mental Health Help-Seeking among Young Adults in Saudi Arabia: A Qualitative Study. Int J Environ Res Public Health. 2022;19:1-11. DOI: 10.3390/ijerph19052848
  20. Shen Y, Tian W, Li N, Niu Y. Comorbidity patterns and implications for disease control: a network analysis of medical records from Shanghai, China. Front Public Health. 2025;13:1516215. DOI: 10.3389/fpubh.2025.1516215
  21. Olson ME, Hornick MG, Stefanski A, Albanna HR, Gjoni A, Hall GD, et al. A biofunctional review of C-reactive protein (CRP) as a mediator of inflammatory and immune responses: differentiating pentameric and modified CRP isoform effects. Front Immunol. 2023;14:1264383. DOI: 10.3389/fimmu.2023.1264383
  22. Dai Q, Zhang G, Wang Y, Ye L, Shi R, Peng L, et al. Cytokine network imbalance in children with B-cell acute lymphoblastic leukemia at diagnosis. Cytokine. 2023;169:156267. DOI: 10.1016/j.cyto.2023.156267
  23. Jorgovanovic D, Song M, Wang L, Zhang Y. Roles of IFN-γ in tumor progression and regression: a review. Biomark Res. 2020;8(1):49. DOI: 10.1186/s40364-020-00228-x
  24. Mercogliano MF, Bruni S, Mauro F, Elizalde PV, Schillaci R. Harnessing Tumor Necrosis Factor Alpha to Achieve Effective Cancer Immunotherapy. Cancers (Basel). 2021;13(3). DOI: 10.3390/cancers13030564
  25. Wedekind MF, Denton NL, Chen CY, Cripe TP. Pediatric Cancer Immunotherapy: Opportunities and Challenges. Paediatr Drugs. 2018;20(5):395-408. DOI: 10.1007/s40272-018-0297-x
  26. Pérez-Figueroa E, Sánchez-Cuaxospa M, Martínez-Soto KA, Sánchez-Zauco N, Medina-Sansón A, Jiménez-Hernández E, et al. Strong inflammatory response and Th1-polarization profile in children with acute lymphoblastic leukemia without apparent infection. Oncol Rep. 2016;35(5):2699-706. DOI: 10.3892/or.2016.4657
  27. Luczyński W, Stasiak-Barmuta A, Krawczuk-Rybak M, Malinowska I, Matysiak M, Mitura-Lesiuk M, et al. [Th1/Th2 balance in acute lymphoblastic leukemia in children]. Przegl Lek. 2004;61(9):919-23. PMID: 1580389
  28. Jing J, Ma Y, Xie Z, Wang B, Chen Y, Chi E, et al. Acute T-cell lymphoblastic leukemia: chimeric antigen receptor technology may offer a new hope. Front Immunol. 2024;15:1410519. DOI: 10.3389/fimmu.2024.1410519
  29. Malard F, Mohty M. Acute lymphoblastic leukaemia. Lancet. 2020;395(10230):1146-62. DOI: 10.1016/S0140-6736(19)33018-1
  30. Wang F, Li Y, Yang Z, Cao W, Liu Y, Zhao L, et al. Targeting IL-17A enhances imatinib efficacy in Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia. Nat Commun. 2024;15(1):203. DOI: 10.1038/s41467-023-44270-3
  31. Huangfu L, Li R, Huang Y, Wang S. The IL-17 family in diseases: from bench to bedside. Signal Transduct Target Ther. 2023;8(1):402. DOI: 10.1038/s41392-023-01620-3
  32. Mills KHG. IL-17 and IL-17-producing cells in protection versus pathology. Nat Rev Immunol. 2023;23(1):38-54. DOI: 10.1038/s41577-022-00746-9
  33. Radwan RE, Darwish A, Elsaid AM, El-kholy WM. Exploring the potential of IL-10 for risk assessment and early intervention in pediatric ALL. BMC Cancer. 2024;24(1):972. DOI: 10.1186/s12885-024-12677-w
  34. Puckett Y, Chan O. Acute Lymphocytic Leukemia. StatPearls. Treasure Island (FL) ineligible companies. Disclosure: Onyee Chan declares no relevant financial relationships with ineligiblecompanies.: StatPearls Publishing.
  35. Glocker EO, Kotlarz D, Klein C, Shah N, Grimbacher B. IL-10 and IL-10 receptor defects in humans. Ann N Y Acad Sci. 2011;1246:102-7. DOI: 10.1111/j.1749-6632.2011.06339.x
How to Cite
Ismael , H. D. ., Tharwat Baban, S., & Amin, Z. A. (2026). The cytokine milieu orchestrates the Th1/Th2/Th17 and Treg cells roles in acute lymphoblastic leukemia patients. Zanco Journal of Medical Sciences (ZJMS), 30(1), 88–104. https://doi.org/10.15218/zjms.2026.007

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