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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2021; 67(4): 86-96

Study of the immunomodulating influence of preparation alpha/beta-defensins on chemo/radiotherapy of patients with oral and oropharyngeal cancer

H.A. Hirna1, D.V. Maltsev2, L.V. Natrus2, M.M. Rozhko1, I.D. Kostyshyn1, I.S. Tanasiychuk1

  1. Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine
  2. Bogomolets National Medical University, Kyiv, Ukraine
DOI: https://doi.org/10.15407/fz67.04.086


Abstract

The state of antitumor immunity of patients with oral cavity and oropharyngeal cancer during treatment (radiation and chemoradiation therapy), which additionally included α/β-defensin immunotherapy, was studied. In all three study groups, where preparation α/β-defensins was used, there was a more pronounced dose-dependent decrease in the relative number of lymphocytes in the blood than among those receiving cytostatic therapy in mono mode. Patients of group I received radiation therapy and immunotherapy, group II - chemoradiation and immunotherapy, group III - radiation therapy with immunotherapy in increased doses, VI - radiation, V - chemoradiation. Thus, in group І the decrease in the absolute number of lymphocytes was by 0.6×109/l, in group II - by 0.82×109/l, and in group III - by 0.93×109/l; by 8.51% there was a decrease in the relative number of lymphocytes in group I, by 15.52% in group II and in group III - by 14.32%. A significant decrease in the absolute number of CD3+ T cells in the blood was registered with a combination of radiation- and immunotherapy: in group I from 1141×106/l to 682×106/l and in group III - from 871×106/l to 309×106/l. At the same time, there was an increase in the relative number of natural killers in the blood of patients undergoing radiation therapy in combination with immunotherapy, also with a dose-dependent effect, the growth in group I is from 16 to 17% and group III - from 13.4 to 19.5%. Among patients undergoing cytostatic therapy, there were significant differences in the absolute number of NKT cells in the combination of radiation and immunotherapy, groups I and III, by reducing the number of these lymphocytes in the blood from 86 to 57 and from 62 to 31, respectively. α/β-defensins have been shown to have a dose-dependent adjuvant effect on cytostatic treatment – radiation, and chemoradiation of patients with cancer of the oral cavity and oropharynx. Simultaneously with the use of the drug α/β-defensins associated additional immunomodulatory effect in the form of the restructuring of the subpopulation of lymphocytes due to an increase in the relative number of natural killers in the blood.

Keywords: immunotherapy; immunomodulation; immunosuppression; adjuvant; natural killer T lymphocytes; antitumor resistance.

Full text: (PDF, in English)

References

  1. Maltsev DV, Girna GA. The deficiency of natural killer cells and/or natural killer T cells as the cause of malignancies (literature review). Clin Oncol. 2018; 8(1): 34-9.
  2. Bron L, Jandus C, Andrejevic-Blant S, et al. Prognostic value of arginase-II expression and regulatory T-cell infiltration in head and neck squamous cell carcinoma. Int J Cancer. 2013; 132 (3): E85-93. CrossRef PubMed
  3. Dasgupta S, Bhattacharya-Chatterjee M, O'Malley JrBW, et al. Inhibition of NK cell activity through TGF-beta 1 by down-regulation of NKG2D in a murine model of head and neck cancer. J Immunol. 2005; 175: 5541-50. CrossRef PubMed
  4. Whiteside TL. Immunobiology of head and neck cancer. Cancer Metast. Rev. 2005; 24: 95-105. CrossRef PubMed
  5. Ferris R, Whiteside TL, Ferrone S. Clinical significance of down regulate dantigen processing machinery in head and neck cancer. Clin Cancer Res. 2006;12:3890-5. CrossRef PubMed
  6. Alcolea S, Anton R, Camacho M, et al. Interaction between head and necksquamous cell carcinoma cells andfibroblasts in the biosynthesis of PGE2. J Lipid Res. 2012; 53(4): 630-42. CrossRef PubMed PubMedCentral
  7. Tsiklauri VT. Immunocorrective therapy in the complex treatment of patients with cancer of the mucous membrane of the oral cavity [author. dis…the degree candidate of Medical Sciences: 14.01.12]. Moscow: Russian Oncology Scientific Center named after NN Blokhin of the Russian Academy of Medical Sciences, 2013; 27 p. [Russian].
  8. Whiteside TL. Tumor-induced death of immune cells: its mechanisms and consequences. Semin Cancer Biol. 2002;12(1):43-50. CrossRef PubMed
  9. Bron L, Jandus C, Andrejevic-Blant S, et al. Prognostic value of arginase-II expression and regulatory T-cellinfiltration in head and neck squamous cell carcinoma. Int J Cancer. 2013; 132(3): E85-93. CrossRef PubMed
  10. Loose D, Signore A, Bonanno E, et al. Prognostic value of CD25 expression onlymphocytes and tumor cells insquamous-cell carcinoma of the head andneck. Cancer Biother Radiopharm. 2008;23(1): 25-33. CrossRef PubMed
  11. Ni XR, Guo CC, Yu YJ, et al. Combination of levetiracetam and IFN-alpha increased temozolomide efficacy in MGMT-positive glioma. Cancer Chemother Pharmacol. 2020;86(6):773-82. CrossRef PubMed
  12. Dafni U, Michielin O, Lluesma SM, et al. Efficacy of adoptive therapy with tumor-infiltrating lymphocytes and recombinant interleukin-2 in advanced cutaneous melanoma: a systematic review and meta-analysis. Ann Oncol. 2019; 30(12):1902-13. CrossRef PubMed
  13. Du D, Song T, Dai H, et al. Stereotactic body radiation therapy and thymosin alpha-1-induced anti-tumor effects in heavily pretreated, metastatic esophageal squamous cell carcinoma patients. Oncoimmunology. 2018; 7(8): e1450128. CrossRef PubMed PubMedCentral
  14. Farin HF, Karthaus WR, Kujala P, et al. Paneth cell extrusion and release of antimicrobial products is directly controlled by immune cell-derived IFN-gamma. J Exp Med. 2014;211(7):1393-405. CrossRef PubMed PubMedCentral
  15. Mei HF, Jin XB, Zhu JY, et al. Beta-defensin 2 as an adjuvant promotes anti-melanoma immune responses and inhibits the growth of implanted murine melanoma in vivo. PLoS One. 2012; 7(2): e31328. CrossRef PubMed PubMedCentral
  16. Zakharenko VV, Naishtetik VYa, Kudryavtseva IG, et al. Pharmacological properties of the drug propes (experimental studies) Oncology. 2004; 6(3):36-7. [Ukrainian].
  17. Mamchur VI, Levykh AE. Defensins - endogenous peptides with anti-infective and anticancer properties (review). Tavricheskiy Med-Biol Vestn 2012; 15(58): 315-21. [Ukrainian].
  18. Litvinenko AA. Implication of the immune correction in the complex treatment of breast cancer. Woman's health. 2012;1(67);134-7. [Ukrainian].
  19. Sivkovich A, Gubareva AA, Pavlenko YuV, et al. Ways to improve the results of combined chemotherapy and radiation therapy in patients with malignant lymphomas. Med Business. 2005;7: 65-9. [Ukrainian].
  20. Hirna HA, Kostyshyn ID, Rozhko MM, et al. Method of chemotherapeutic potentiation in radiation therapy of patients with oral cancer: Patent. 142686 Ukraina. No. u201911428; Declared. 25.11.2019; published.25.06.2020, Bul. No. 12. 3 r. [Ukrainian].
  21. Zhou L, Pan LC, Zheng YG, et al. Novel strategy of sirolimus plus thymalfasin and huaier granule on tumor recurrence of hepatocellular carcinoma beyond the UCSF criteria following liver transplantation: A single center experience. Oncol Lett. 2018;16(4): 4407-17. CrossRef PubMed PubMedCentral
  22. Ballas ZK, Turner JM, Turner DA, et al. A patient with simultaneous absence of "classical" natural killer cells (CD3-, CD16+, and NKH1+) and expansion of CD3+, CD4-, CD8-, NKH1+ subset. J Allergy Clin Immunol. 1990; 85(2): 453-9. CrossRef
  23. Imashuku S, Hyakuna N, Funabiki T, et al. Low natural killer activity and central nervous system disease as a high-risk prognostic indicator in young patients with hemophagocytic lymphohistiocytosis. Cancer. 2002;94(11):3023-31. CrossRef PubMed
  24. Holtan SG, Creedon DJ, Thompson MA, et al. Expansion of CD16-negative natural killer cells in the peripheral blood of patients with metastatic melanoma. Clin Dev Immunol. 2011;2011:316314. CrossRef PubMed PubMedCentral
  25. Machaczka M, Klimkowska M, Chiang SC, et al. Development of classical Hodgkin's lymphoma in an adult with biallelic STXBP2 mutations. Haematologica. 2013;98(5):760-4. CrossRef PubMed PubMedCentral
  26. Shaw RK, Issekutz AC, Fraser R, et al. Bilateral adrenal EBV-associated smooth muscle tumors in a child with a natural killer cell deficiency. Blood. 2012;119(17):4009-12. CrossRef PubMed PubMedCentral
  27. Rafei H, Daher M, Rezvani K. Chimeric antigen receptor (CAR) natural killer (NK)-cell therapy: leveraging the power of innate immunity. Br J Haematol. 2020. 20. CrossRef PubMed
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