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Implications of IL-21 in solid tumor therapy

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Abstract

Cancer, the most deadly disease, is known as a recent dilemma worldwide. Presently different treatments are used for curing cancers, especially solid cancers. Because of the immune-enhancing functions of cytokine, IL-21 as a cytokine may have new possibilities to manipulate the immune system in disease conditions, as it stimulates NK and CTL functions and drives IgG antibody production. Indeed, IL-21 has been revealed to elicit antitumor-immune responses in several tumor models. Combining IL-21 with other agents, which target tumor cells, immune-regulatory circuits, or other immune-enhancing molecules enhances this activity. The exciting breakthrough in the results obtained in pre-clinical situations has led to the early outset of present developing clinical trials in cancer patients. In the paper, we have reviewed the function of IL-21 in solid tumor immunotherapy.

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Abbreviations

IL-21:

Interleukin-21

IL-21R:

IL-21 receptor

rIL-21:

recombinant IL-21

γc:

γ chain

TAA:

tumor-associated antigen

mAbs:

Monoclonal antibody

HSCTs:

Hematopoietic stem cell transplants

DDS:

Drug Delivery Systems

RT:

Radiation Therapy

Trimab:

triple antibody cocktail

ACT:

Adoptive cell transfer

IFN-γ:

interferon gamma

GM-CSF:

Granulocyte–macrophage colony-stimulating factor

PTB:

phosphotyrosine binding

GC:

germinal center

Jak1:

Janus kinase 1

Jak3:

Janus kinase 3

STAT:

signal transducer and activator of transcription

MAPK:

mitogen-activated protein kinase

PI3K:

phosphoinositide 3-kinase

BCL-6:

B-cell lymphoma 6

Anti-DR5:

Anti-death receptor 5

WHO:

World Health Organization

NKT cell:

Natural killer T cell

NK cell:

Natural killer cell

B cell:

B lymphocytes

T cell:

T lymphocytes

DC cell:

Dendritic cell

PC cell:

plasma cell

TFH:

follicular helper T

Breg:

regulatory B cell

Treg:

regulatory T cell

ESO:

Eosinophils

Mas cell:

mast cell

Mq:

macrophage cell

Epi cell:

epithelial cell

ADCC:

Antibody-Dependent Cellular Cytotoxicity

MMP:

matrix metalloproteinase

MIP3α:

macrophage-inflammatory protein 3α

TRAIL:

TNF-depended death-stimulating ligand

PD-1:

Programmed Death-1

CTL cell:

Cytotoxic T cell

MART-1:

melanoma antigen recognized by T cells 1

DTIC:

dacarbazine

RCC:

renal cell carcinoma

WT1:

Wilms tumor gene 1

NKG2D:

natural killer group 2 member D

MCL:

Mantle Cell Lymphoma

NB:

neuroblastoma

References

  1. Mileo AM, Miccadei S. Polyphenols as modulator of oxidative stress in cancer disease: new therapeutic strategies. Oxid Med Cell Longev 2016. 2016. https://doi.org/10.1155/2016/6475624.

    Article  Google Scholar 

  2. Vicente-Dueñas C, Hauer J, Ruiz-Roca L, Ingenhag D, Rodríguez-Meira A, Auer F, Borkhardt A, Sánchez-García I. Tumoral stem cell reprogramming as a driver of cancer: theory, biological models, implications in cancer therapy. Semin Cancer Biol. 2015;32:3–9.

    PubMed  Google Scholar 

  3. Hahn WC, Weinberg RA. Rules for making human tumor cells. N Engl J Med. 2002;347(20):1593–603.

    CAS  PubMed  Google Scholar 

  4. Peltomäki P. Mutations and epimutations in the origin of cancer. Exp Cell Res. 2012;318(4):299–310.

    PubMed  Google Scholar 

  5. Mehta DS, Wurster AL, Grusby MJ. Biology of IL-21 and the IL-21 receptor. Immunol Rev. 2004;202(1):84–95.

    CAS  PubMed  Google Scholar 

  6. Haikerwal SJ, Hagekyriakou J, MacManus M, Martin OA, Haynes NM. Building immunity to cancer with radiation therapy. Cancer Lett. 2015;368(2):198–208.

    CAS  PubMed  Google Scholar 

  7. DeNardo DG, Johansson M, Coussens LM. Immune cells as mediators of solid tumor metastasis. Cancer Metastasis Rev. 2008;27(1):11–8.

    CAS  PubMed  Google Scholar 

  8. Cho D, Shook DR, Shimasaki N, Chang Y-H, Fujisaki H, Campana D. Cytotoxicity of activated natural killer cells against pediatric solid tumors. Clin Cancer Res. 2010;16(15):3901–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. DeSantis CE, Kramer JL, Jemal A. The burden of rare cancers in the United States. Cancer J Clin. 2017;67(4):261–72.

    Google Scholar 

  10. Patel A. Benign vs malignant tumors. JAMA Oncol. 2020;6(9):1488.

    PubMed  Google Scholar 

  11. Thakur NA, Daniels AH, Schiller J, Valdes MA, Czerwein JK, Schiller A, Esmende S, Terek RM. Benign tumors of the spine. J Am Acad Orthop Surg. 2012;20(11):715–24.

    PubMed  Google Scholar 

  12. Millet I, Doyon FC, Hoa D, Thuret R, Merigeaud S, Serre I, Taourel P. Characterization of small solid renal lesions: can benign and malignant tumors be differentiated with CT? Am J Roentgenol. 2011;197(4):887–96.

    Google Scholar 

  13. Hudzik B, Miszalski-Jamka K, Glowacki J, Lekston A, Gierlotka M, Zembala M, Polonski L, Gasior M. Malignant tumors of the heart. Cancer Epidemiol. 2015;39(5):665–72.

    PubMed  Google Scholar 

  14. Gavhane Y, Shete A, Bhagat A, Shinde V, Bhong K, Khairnar G, Yadav A. Solid tumors: facts, challenges and solutions. Int J Pharma Sci Res. 2011;2(1):1–12.

    Google Scholar 

  15. Chen Y-P, Zhang Y, Lv J-W, Li Y-Q, Wang Y-Q, He Q-M, Yang X-J, Sun Y, Mao Y-P, Yun J-P. Genomic analysis of tumor microenvironment immune types across 14 solid cancer types: immunotherapeutic implications. Theranostics. 2017;7(14):3585.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Ranuncolo SM. Liquid biopsy in liquid tumors. J Cancer Ther. 2017;8(3):302–20.

    CAS  Google Scholar 

  17. Kather JN, Suarez-Carmona M, Charoentong P, Weis C-A, Hirsch D, Bankhead P, Horning M, Ferber D, Kel I, Herpel E. Topography of cancer-associated immune cells in human solid tumors. Elife. 2018;7: e36967.

    PubMed  PubMed Central  Google Scholar 

  18. Giamas G, Man YL, Hirner H, Bischof J, Kramer K, Khan K, Ahmed SSL, Stebbing J, Knippschild U. Kinases as targets in the treatment of solid tumors. Cell Signal. 2010;22(7):984–1002.

    CAS  PubMed  Google Scholar 

  19. Zhukov N, Tjulandin S. Targeted therapy in the treatment of solid tumors: practice contradicts theory. Biochem Mosc. 2008;73(5):605–18.

    CAS  Google Scholar 

  20. Parizi PK, Yarahmadi F, Tabar HM, Hosseini Z, Sarli A, Kia N, Tafazoli A, Esmaeili S-A. MicroRNAs and target molecules in bladder cancer. Med Oncol. 2020;37:1–33.

    Google Scholar 

  21. Travis LB. Therapy-associated solid tumors. Acta Oncol. 2002;41(4):323–33.

    PubMed  Google Scholar 

  22. Esmaeili S-A, Nejatollahi F, Sahebkar A. Inhibition of intercellular communication between prostate cancer cells by a specific anti-STEAP-1 single chain antibody. Anti-Cancer Agents Med Chem. 2018;18(12):1674–9.

    CAS  Google Scholar 

  23. Fuchs J. The role of minimally invasive surgery in pediatric solid tumors. Pediatr Surg Int. 2015;31(3):213–28.

    PubMed  Google Scholar 

  24. Orosco RK, Tapia VJ, Califano JA, Clary B, Cohen EE, Kane C, Lippman SM, Messer K, Molinolo A, Murphy JD. Positive surgical margins in the 10 most common solid cancers. Sci Rep. 2018;8(1):1–9.

    CAS  Google Scholar 

  25. Graham K, Unger E. Overcoming tumor hypoxia as a barrier to radiotherapy, chemotherapy and immunotherapy in cancer treatment. Int J Nanomed. 2018;13:6049.

    CAS  Google Scholar 

  26. Nadeem H, Jayakrishnan TT, Rajeev R, Johnston FM, Gamblin TC, Turaga KK, Nadeem H, Jayakrishnan TT, Rajeev R, Johnston FM. ReCAP: Cost differential of chemotherapy for solid tumors. J Oncol Pract. 2016;12(3):251–251.

    PubMed  Google Scholar 

  27. Maughan BL, Antonarakis ES. Androgen pathway resistance in prostate cancer and therapeutic implications. Expert Opin Pharmacother. 2015;16(10):1521–37.

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Ehrhardt MJ, Brazauskas R, He W, Rizzo JD, Shaw BE. Survival of patients who develop solid tumors following hematopoietic stem cell transplantation. Bone Marrow Transpl. 2016;51(1):83–8.

    CAS  Google Scholar 

  29. Parakh S, Parslow AC, Gan HK, Scott AM. Antibody-mediated delivery of therapeutics for cancer therapy. Expert Opin Drug Deliv. 2016;13(3):401–19.

    CAS  PubMed  Google Scholar 

  30. Feng Z, Yi X, Hajavi J. New and old adjuvants in allergen-specific immunotherapy: with a focus on nanoparticles. J Cell Physiol. 2021;236(2):863–76.

    CAS  PubMed  Google Scholar 

  31. Khakzad MR, Hajavi J, Sadeghdoust M, Aligolighasemabadi F. Effects of lipopolysaccharide-loaded PLGA nanoparticles in mice model of asthma by sublingual immunotherapy. Int J Polym Mater Polym Biomater. 2019. https://doi.org/10.1080/00914037.2018.1561453.

    Article  Google Scholar 

  32. Khawar IA, Kim JH, Kuh H-J. Improving drug delivery to solid tumors: priming the tumor microenvironment. J Control Release. 2015;201:78–89.

    CAS  PubMed  Google Scholar 

  33. Wicki A, Witzigmann D, Balasubramanian V, Huwyler J. Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications. J Control Release. 2015;200:138–57.

    CAS  PubMed  Google Scholar 

  34. Wolchok JD, Hoos A, O’Day S, Weber JS, Hamid O, Lebbé C, Maio M, Binder M, Bohnsack O, Nichol G. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009;15(23):7412–20.

    CAS  PubMed  Google Scholar 

  35. Jung N-C, Lee J-H, Chung K-H, Kwak YS, Lim D-S. Dendritic cell-based immunotherapy for solid tumors. Transl Oncol. 2018;11(3):686–90.

    PubMed  PubMed Central  Google Scholar 

  36. Mobarez AM, Soleimani N, Esmaeili S-A, Farhangi B. Nanoparticle-based immunotherapy of breast cancer using recombinant Helicobacter pylori proteins. Eur J Pharm Biopharm. 2020;155:69–76.

    Google Scholar 

  37. Esmaeili S-A, Hajavi J. The role of indoleamine 2, 3-dioxygenase in allergic disorders. Mol Biol Rep. 2022;49:1–10.

    Google Scholar 

  38. Kumar S, Chandra D. A therapeutic perspective of cytokines in tumor management. Inflamm Cell Signal. 2014;1(2):1–5.

    Google Scholar 

  39. Kim-Schulze S, Kim HS, Fan Q, Kim DW, Kaufman HL. Local IL-21 promotes the therapeutic activity of effector T cells by decreasing regulatory T cells within the tumor microenvironment. Mol Ther. 2009;17(2):380–8.

    CAS  PubMed  Google Scholar 

  40. Santegoets SJ, Turksma AW, Powell DJ Jr, Hooijberg E, de Gruijl TD. IL-21 in cancer immunotherapy: at the right place at the right time. Oncoimmunology. 2013;2(6): e24522.

    PubMed  PubMed Central  Google Scholar 

  41. Shiao SL, Ganesan AP, Rugo HS, Coussens LM. Immune microenvironments in solid tumors: new targets for therapy. Genes Dev. 2011;25(24):2559–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Cruz E, Kayser V. Monoclonal antibody therapy of solid tumors: clinical limitations and novel strategies to enhance treatment efficacy. Biologics. 2019;13:33.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Neves H, Kwok HF. Recent advances in the field of anti-cancer immunotherapy. BBA Clin. 2015;3:280–8.

    PubMed  PubMed Central  Google Scholar 

  44. Fajgenbaum DC, June CH. Cytokine storm. N Engl J Med. 2020;383(23):2255–73.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Doulabi H, Masoumi E, Rastin M, Azarnaminy AF, Esmaeili S-A, Mahmoudi M. The role of Th22 cells, from tissue repair to cancer progression. Cytokine. 2022;149: 155749.

    CAS  PubMed  Google Scholar 

  46. Lee S, Margolin K. Cytokines in cancer immunotherapy. Cancers. 2011;3(4):3856–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Brandt K, Singh PB, Bulfone-Paus S, Rückert R. Interleukin-21: a new modulator of immunity, infection, and cancer. Cytokine Growth Factor Rev. 2007;18(3):223–32.

    CAS  PubMed  Google Scholar 

  48. Pulliam SR, Uzhachenko RV, Adunyah SE, Shanker A. Common gamma chain cytokines in combinatorial immune strategies against cancer. Immunol Lett. 2016;169:61–72.

    CAS  PubMed  Google Scholar 

  49. Davis ID, Brady B, Kefford RF, Millward M, Cebon J, Skrumsager BK, Mouritzen U, Hansen LT, Skak K, Lundsgaard D. Clinical and biological efficacy of recombinant human interleukin-21 in patients with stage IV malignant melanoma without prior treatment: a phase IIa trial. Clin Cancer Res. 2009;15(6):2123–9.

    CAS  PubMed  Google Scholar 

  50. Davis ID, Skak K, Smyth MJ, Kristjansen PE, Miller DM, Sivakumar PV. Interleukin-21 signaling: functions in cancer and autoimmunity. Clin Cancer Res. 2007;13(23):6926–32.

    CAS  PubMed  Google Scholar 

  51. Davis ID, Skrumsager BK, Cebon J, Nicholaou T, Barlow JW, Moller NPH, Skak K, Lundsgaard D, Frederiksen KS, Thygesen P. An open-label, two-arm, phase I trial of recombinant human interleukin-21 in patients with metastatic melanoma. Clin Cancer Res. 2007;13(12):3630–6.

    CAS  PubMed  Google Scholar 

  52. Zeng R, Spolski R, Casas E, Zhu W, Levy DE, Leonard WJ. The molecular basis of IL-21–mediated proliferation. Blood. 2007;109(10):4135–42.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Pène J, Gauchat J-F, Lécart S, Drouet E, Guglielmi P, Boulay V, Delwail A, Foster D, Lecron J-C, Yssel H. Cutting edge: IL-21 is a switch factor for the production of IgG1 and IgG3 by human B cells. J Immunol. 2004;172(9):5154–7.

    PubMed  Google Scholar 

  54. Zotos D, Coquet JM, Zhang Y, Light A, D’Costa K, Kallies A, Corcoran LM, Godfrey DI, Toellner K-M, Smyth MJ. IL-21 regulates germinal center B cell differentiation and proliferation through a B cell–intrinsic mechanism. J Exp Med. 2010;207(2):365–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Davis MR, Zhu Z, Hansen DM, Bai Q, Fang Y. The role of IL-21 in immunity and cancer. Cancer Lett. 2015;358(2):107–14.

    CAS  PubMed  Google Scholar 

  56. Saied A, Pillarisetty VG, Katz SC. Immunotherapy for solid tumors—a review for surgeons. J Surg Res. 2014;187(2):525–35.

    CAS  PubMed  Google Scholar 

  57. Ettinger R, Kuchen S, Lipsky PE. The role of IL-21 in regulating B-cell function in health and disease. Immunol Rev. 2008;223(1):60–86.

    CAS  PubMed  Google Scholar 

  58. Søndergaard H, Skak K. IL-21: roles in immunopathology and cancer therapy. Tissue Antigens. 2009;74(6):467–79.

    PubMed  Google Scholar 

  59. Denman CJ, Senyukov VV, Somanchi SS, Phatarpekar PV, Kopp LM, Johnson JL, Singh H, Hurton L, Maiti SN, Huls MH. Membrane-bound IL-21 promotes sustained ex vivo proliferation of human natural killer cells. PLoS ONE. 2012;7(1): e30264.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Monteleone G, Pallone F, Macdonald TT. Interleukin-21 as a new therapeutic target for immune-mediated diseases. Trends Pharmacol Sci. 2009;30(8):441–7.

    CAS  PubMed  Google Scholar 

  61. Croce M, Rigo V, Ferrini S. IL-21: a pleiotropic cytokine with potential applications in oncology. J Immunol Res. 2015;2015:1–15.

    Google Scholar 

  62. Spolski R, Kim H-P, Zhu W, Levy DE, Leonard WJ. IL-21 mediates suppressive effects via its induction of IL-10. J Immunol. 2009;182(5):2859–67.

    CAS  PubMed  Google Scholar 

  63. Li Y, Bleakley M, Yee C. IL-21 influences the frequency, phenotype, and affinity of the antigen-specific CD8 T cell response. J Immunol. 2005;175(4):2261–9.

    CAS  PubMed  Google Scholar 

  64. Singh H, Figliola MJ, Dawson MJ, Huls H, Olivares S, Switzer K, Mi T, Maiti S, Kebriaei P, Lee DA. Reprogramming CD19-specific T cells with IL-21 signaling can improve adoptive immunotherapy of B-lineage malignancies. Can Res. 2011;71(10):3516–27.

    CAS  Google Scholar 

  65. Chapuis AG, Ragnarsson GB, Nguyen HN, Chaney CN, Pufnock JS, Schmitt TM, Duerkopp N, Roberts IM, Pogosov GL, Ho WY. Transferred WT1-reactive CD8+ T cells can mediate antileukemic activity and persist in post-transplant patients. Sci Transl Med. 2013;5(174):174ra27-174ra27.

    PubMed  PubMed Central  Google Scholar 

  66. Takaki R, Hayakawa Y, Nelson A, Sivakumar PV, Hughes S, Smyth MJ, Lanier LL. IL-21 enhances tumor rejection through a NKG2D-dependent mechanism. J Immunol. 2005;175(4):2167–73.

    CAS  PubMed  Google Scholar 

  67. Wang G, Tschoi M, Spolski R, Lou Y, Ozaki K, Feng C, Kim G, Leonard WJ, Hwu P. In vivo antitumor activity of interleukin 21 mediated by natural killer cells. Can Res. 2003;63(24):9016–22.

    CAS  Google Scholar 

  68. Brady J, Hayakawa Y, Smyth MJ, Nutt SL. IL-21 induces the functional maturation of murine NK cells. J Immunol. 2004;172(4):2048–58.

    CAS  PubMed  Google Scholar 

  69. Huarte E, Fisher J, Turk MJ, Mellinger D, Foster C, Wolf B, Meehan KR, Fadul CE, Ernstoff MS. Ex vivo expansion of tumor specific lymphocytes with IL-15 and IL-21 for adoptive immunotherapy in melanoma. Cancer Lett. 2009;285(1):80–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Chow MT, Luster AD. Chemokines in cancer. Cancer Immunol Res. 2014;2(12):1125–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Chapuis AG, Lee SM, Thompson JA, Roberts IM, Margolin KA, Bhatia S, Sloan HL, Lai I, Wagener F, Shibuya K. Combined IL-21–primed polyclonal CTL plus CTLA4 blockade controls refractory metastatic melanoma in a patient. J Exp Med. 2016;213(7):1133–9.

    PubMed  PubMed Central  Google Scholar 

  72. Zhao Y, Zhang Z, Lei W, Wei Y, Ma R, Wen Y, Wei F, Fan J, Xu Y, Chen L. IL-21 is an accomplice of PD-L1 in the induction of PD-1-Dependent treg generation in head and neck cancer. Front Oncol. 2021;11: 648293.

    CAS  PubMed  PubMed Central  Google Scholar 

  73. Petrella TM, Tozer R, Belanger K, Savage KJ, Wong R, Smylie M, Kamel-Reid S, Tron V, Chen BE, Hunder NN. Interleukin-21 has activity in patients with metastatic melanoma: a phase II study. J Clin Oncol. 2012;30(27):3396–401.

    CAS  PubMed  Google Scholar 

  74. Steele N, Anthony A, Saunders M, Esmarck B, Ehrnrooth E, Kristjansen P, Nihlén A, Hansen L, Cassidy J. A phase 1 trial of recombinant human IL-21 in combination with cetuximab in patients with metastatic colorectal cancer. Br J Cancer. 2012;106(5):793–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Elishmereni M, Kheifetz Y, Søndergaard H, Overgaard RV, Agur Z. An integrated disease/pharmacokinetic/pharmacodynamic model suggests improved interleukin-21 regimens validated prospectively for mouse solid cancers. PLoS Comput Biol. 2011;7(9): e1002206.

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Timmerman JM, Byrd JC, Andorsky DJ, Yamada RE, Kramer J, Muthusamy N, Hunder N, Pagel JM. A phase I dose-finding trial of recombinant interleukin-21 and rituximab in relapsed and refractory low grade B-cell lymphoproliferative disorders. Clin Cancer Res. 2012;18(20):5752–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Bhatt S, Matthews J, Parvin S, Sarosiek KA, Zhao D, Jiang X, Isik E, Letai A, Lossos IS. Direct and immune-mediated cytotoxicity of interleukin-21 contributes to antitumor effects in mantle cell lymphoma. Blood. 2015;126(13):1555–64.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Rigo V, Corrias MV, Orengo AM, Brizzolara A, Emionite L, Fenoglio D, Filaci G, Croce M, Ferrini S. Recombinant IL-21 and anti-CD4 antibodies cooperate in syngeneic neuroblastoma immunotherapy and mediate long-lasting immunity. Cancer Immunol Immunother. 2014;63(5):501–11.

    CAS  PubMed  Google Scholar 

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Acknowledgements

The authors appreciate the cooperation of Mashhad University of Medical Sciences.

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Authors and Affiliations

  1. Department of Medical Sciences of Laboratory, Infectious Diseases Research Center, School of Para-Medicine, Gonabad University of Medical Sciences, Gonabad, Iran

    Seyed Hossein Abtahi Eivary

  2. Medical Laboratory Science Department, College of Science, University of Raparin, Rania, Sulaymaniyah, Iraq

    Ramiar Kamal Kheder

  3. Department of Medical Analysis, Faculty of Applied Science, Tishk International University, Erbil, Iraq

    Soran K. Najmaldin

  4. Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Nahid Kheradmand

  5. Immunology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

    Seyed-Alireza Esmaeili

  6. Immunology Department, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Seyed-Alireza Esmaeili

  7. Department of Basic Sciences, Faculty of Medicine, Infectious Diseases Research Center, Gonabad University of Medical Science, Gonabad, Iran

    Jafar Hajavi

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  1. Seyed Hossein Abtahi Eivary
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Eivary, S.H.A., Kheder, R.K., Najmaldin, S.K. et al. Implications of IL-21 in solid tumor therapy. Med Oncol 40, 191 (2023). https://doi.org/10.1007/s12032-023-02051-4

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