The type of cytokines production that regulate NK activity in women with uterine leiomyoma
Abstract
Introduction. Natural killer cells (NK) play an important role in the regulation of tumor growth. The control of NK activity is largely carried out by the microenvironment, in which cytokines play the main role.
The aim of the study was to evaluate the effect of IL–18, IL-27 and IL-35 regulating NK function in women with uterine leiomyoma (LMM).
Material and methods. The study involved 51 womens of reproductive age with symptomatic intramural LMM and 12 practically healthy women without this pathology. The level of cytokines IL-18, IL-27 and IL-35 in peripheral blood serum, endometrial tissue and myomatous nodes lysates was assessed by enzyme immunoassay.
Results. In women with LMM, the serum IL-18 level was lower compared to women without LMM. IL-27 in serum was detected only in 20/51 (39.2%) women with LMM. Women of reproductive age with LMM were characterized by a higher level of IL-27 in endometrial tissues than women without LMM. In the tissues of myomatous nodes, lower levels of all studied cytokines regulating the activity of NK were detected in comparison with those in the endometrium.
Conclusion. The presence of myomatous nodes affects the production of cytokines regulating the activation of NK in endometrial tissues, however, in the tissues of the myomatous nodes themselves, the production of cytokines, both with activating and inhibitory activity involved in the regulation of NK function, remains relatively low.
Keywords:uterine leiomyoma; cytokines; IL-18; IL-27; IL-35; natural killers
For citation: Sotnikova N.Yu., Malyshkina D.A., Voronin D.N. The type of cytokines production that regulate NK activity in women with uterine leiomyoma. Immunologiya. 2023; 44 (2): 202–8. DOI: https://doi.org/10.33029/0206-4952-2023-44-2-202-208 (in Russian)
Funding. The study had no sponsor support.
Conflict of interests. The authors declare no conflict of interests.
Authors’ contribution. The concept and design of the study – Sotnikova N.Yu.; collection and processing of material – Malyshkina D.A., Voronin D.N.; statistical processing – Sotnikova N.Yu., Malyshkina D.A., Voronin D.N.; writing the text – Sotnikova N.Yu., Voronin D.N.; editing, approval of the final version of the article, responsibility for the integrity of all parts of the article – Sotnikova N.Yu., Malyshkina D.A., Voronin D.N.
References
1. Konjeviс G.M., Vuletiс A.M., Mirjaсiс Martinoviс K.M., Jurisic V.B. The role of cytokines in the regulation of NK cells in the tumor environment. Cytokine. 2019; 117: 30–40. DOI: https://www.doi.org/10.1016/j.cyto.2019.02.001
2. Khamatova A.A., Chebotareva T.A., Balmasova I.P. Tissue-resident natural killer cells: features of functioning in the uterus and decidual membrane. Immunologiya. 2021; 42 (5): 574–80. DOI: https://doi.org/10.33029/0206-4952-2021-42-5-574-580 (in Russian)
3. Barrow A.D., Edeling M.A., Trifonov V., Luo J., et al. Natural Killer Cells Control Tumor Growth by Sensing a Growth Factor. Cell. 2018; 172 (3): 534–48. DOI: https://www.doi.org/10.1016/j.cell.2017.11.037
4. Montaldo E., Vacca P., Vitale C., Moretta F., et al. Human innate lymphoid cells. Immunol Lett. 2016; 179: 2–8. DOI: https://www.doi.org/10.1016/j.imlet.2016.01.007
5. Lanier L.L., Le A.M., Civin C.I., Loken M.R., et al. The relationship of CD16 (Leu-11) and Leu-19 (NKH-1) antigen expression on human peripheral blood NK cells and cytotoxic T lymphocytes. J Immunol. 1986; 136 (12): 4480–6. DOI: https://www.doi.org/doi.org/10.4049/jimmunol.136.12.4480
6. Cooper M.A., Fehniger T.A., Caligiuri M.A. Review. The biology of human natural killer-cell subsets. Trends in Immunology. 2001; 22 (11): 633–40. DOI: https://www.doi.org/10.1016/s1471-4906(01)02060-9
7. Min-Oo G., Kamimura Y., Hendricks D.W., Nabekura T., et al. Natural killer cells: walking three paths down memory lane. Trends Immunol. 2013; 34 (6): 251–8. DOI: https://www.doi.org/10.1016/j.it.2013.02.005
8. Stojanovic A., Correia M.P., Cerwenka A. Shaping of NK cell responses by the tumor microenvironment. Cancer Microenviron. 2013; 6 (2): 135–46. DOI: https://www.doi.org/10.1007/s12307-012-0125-8
9. Zwirner N.W., Domaica C.I. Cytokine regulation of natural killer cell effector functions. Biofactors. 2010; 36 (4): 274–88. DOI: https://www.doi.org/10.1002/biof.107
10. Khalil M., Wang D., Hashemi E., Terhune S.S., et al. Implications of a Third signal in NK cells. Cells. 2021; 10 (8): 1955. DOI: https://www.doi.org/10.3390/cells10081955
11. Okamura H., Tsutsi H., Komatsu T., Yutsudo M. Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature. 1995; 37 8 (6552): 88–91. DOI: https://www.doi.org/10.1038/378088a0
12. Lee J.K., Kim S.H., Lewis E.C., Azam T., et al. Differences in signaling pathways by IL-1beta and IL-18. Proc Natl Acad Sci U S A. 2004; 101 (23): 8815–20. DOI: https://www.doi.org/10.1073/pnas.0402800101
13. Terme M., Ullrich E., Aymeric L., Meinhardt K., et al. Cancer-induced immunosuppression: IL-18-elicited immunoablative NK cells. Cancer Res. 2012; 72 (11): 2757–67. DOI: https://www.doi.org/10.1158/0008-5472.CAN-11-3379
14. Zwirner N.W., Ziblat A. Regulation of NK cell activation and effector functions by the IL-12 family of cytokines: The Case of IL-27. Front Immunol. 2017; 8: 25. DOI: https://www.doi.org/10.3389/fimmu.2017.00025
15. Wang R., Jaw J.J., Stutzman N.C., Zou Z., et al. Natural killer cell-produced IFN-γ and TNF-α induce target cell cytolysis through up-regulation of ICAM-1. J Leukoc Biol. 2012; 91 (2): 299–309. DOI: https://www.doi.org/10.1189/jlb.0611308
16. Choi Y.H., Lim E.J., Kim S.W., Moon Y.W. et al. IL-27 enhances IL-15/IL-18-mediated activation of human natural killer cells. J Immunother Cancer. 2019; 7 (1): 168. DOI: https://www.doi.org/10.1186/s40425-019-0652-7
17. Pot C., Apetoh L., Awasthi A., Kuchroo V.K. Induction of regulatory Tr1 cells and inhibition of T(H)17 cells by IL-27. Semin Immunol. 2011; 23 (6): 438–45. DOI: https://www.doi.org/10.1016/j.smim.2011.08.003
18. Mirlekar B., Pylayeva-Gupta Y. IL-12 Family cytokines in cancer and immunotherapy. Cancers (Basel). 2021; 13 (2): 167. DOI: https://www.doi.org/10.3390/cancers13020167
19. Collison L.W., Delgoffe G.M., Guy C.S., Vignali K.M., et al. The composition and signaling of the IL-35 receptor are unconventional. Nat Immunol. 2012; 13 (3): 290–9. DOI: https://www.doi.org/10.1038/ni.2227
20. Collison L.W., Vignali D.A. Interleukin-35: odd one out or part of the family? Immunol Rev. 2008; 226: 248–62. DOI: https://www.doi.org/10.1111/j.1600-065X.2008.00704.x
21. Olson B.M., Sullivan J.A., Burlingham W.J. Interleukin 35: a key mediator of suppression and the propagation of infectious tolerance. Front Immunol. 2013; 4: 315. DOI: https://www.doi.org/10.3389/fimmu.2013.00315
22. Zhang N., Dai H., Dong X., Liu W., et al. Level of interleukin-35 in patients with idiopathic membranous nephropathy and its predictive value for remission time. Frontiers in Immunology. 2022; 926: 368–81. DOI: https://www.doi.org/10.3389/fimmu.2022.926368
23. Liu K., Huang A., Nie J., Tan J., et al. IL-35 Regulates the Function of Immune Cells in Tumor Microenvironment. Front Immunol. 2021; 12: 683332. DOI: https://www.doi.org/10.3389/fimmu.2021.683332
24. Wu H., Li P., Shao N., Ma J., et al. Aberrant expression of Treg-associated cytokine IL-35 along with IL-10 and TGF-β in acute myeloid leukemia. Oncol Lett. 2012; 3 (5): 1119–23. DOI: https://www.doi.org/10.3892/ol.2012.614
25. Gu X., Tian T., Zhang B., Liu Y., et al. Elevated plasma interleukin-35 levels predict poor prognosis in patients with non-small cell lung cancer. Tumour Biol. 2015; 36 (4): 2651–6. DOI: https://www.doi.org/10.1007/s13277-014-2887-8
26. Malyshkina A.I., Voskresenskaya D.L., Voronin D.N., Antsiferova Y.A., et al. Immune mechanisms of regulating the growth of uterine leiomyoma. Akusherstvo i Ginekologiya. 2020; 2: 111–115. DOI://dx.doi.org/10.18565/aig.2020.2.111-115. (in Russian)
27. Fehniger T.A., Cooper M.A. Harnessing NK cell memory for cancer immunotherapy. Trends Immunol. 2016; 37 (12): 877–88. DOI: https://www.doi.org/10.1016/j.it.2016.09.005
28. Ames E., Murphy W.J. Advantages and clinical applications of natural killer cells in cancer immunotherapy. Cancer Immunol Immunother. 2014; 63 (1): 21–8. DOI: https://www.doi.org/10.1007/s00262-013-1469-8
29. Romee R., Rosario M., Berrien-Elliott M.M., Wagner J.A., et al. Cytokine-induced memory-like natural killer cells exhibit enhanced responses against myeloid leukemia. Sci Transl Med. 2016; 8 (357): 357ra123. DOI: https://www.doi.org/10.1126/scitranslmed.aaf2341
30. Vacchelli E., Bloy N., Aranda F., Buquуe A., et al. Trial Watch: Immunotherapy plus radiation therapy for oncological indications. Oncoimmunology. 2016; 5 (9): e1214790. DOI: https://www.doi.org/10.1080/2162402X.2016.1214790
31. Setrerrahmane S., Xu H. Tumor-related interleukins: old validated targets for new anti-cancer drug development. Mol Cancer. 2017; 16 (1): 153. DOI: https://www.doi.org/10.1186/s12943-017-0721-9. PMID: 28927416