Features of the Composition of Cytokines of Various Biological Effects in Patients with Uveal Melanoma: Local Changes in the Lacrimal Fluid. Part 1
https://doi.org/10.18008/1816-5095-2022-1-156-166
Abstract
Purpose. Conduct an extended analysis of the cytokine status and its role in inflammatory processes in uveal melanoma based on multiplex analysis of the tear fluid.
Patients and methods. Immunological studies of blood serum and lacrimal fluid were performed in 80 patients with uveal melanoma and 38 healthy donors (control group). The average age of the surveyed was 53.7 ± 12.2 years. Group 1 included 32 patients with small-sized choroidal melanoma (T1NoMo), group 2 consisted of 26 patients with medium-sized lesions (T2NoMo), group 3 — 22 patients with large tumor sizes (T3NoMo). The cytokine content in the tear fluid was determined by the method of multiplex analysis on the xMAP platform in the Luminex xPONENT 3.1 software using 47 plex kits (ProcartaPlex, eBioscience, Austria).
Results. In the lacrimal fluid of the patient and the paired eye — an increase in pro-inflammatory (IL-1α, IL-2, IL-6, IL-17A, IL-18, TNF-α, MCP-1, MIP-1α, RANTES, GRO-α, IL-8, IP-10), anti-inflammatory (IL-1RA, IL-4, IL-10, IL-5, TGF-1β), proliferative (FGF-2, HGF, IL-15, PDGF-BB, Eotaxin), pro-tumor (NGF-β, IL-7), antitumor (IL-21), angiogenic (VEGF-A, SDF-1α) cytokines in the initial stage of uveal melanoma compared with the control group, p < 0.05.
Conclusion. In response to the manifestation and growth of uveal melanoma, many chemoattractant mediators are produced, including pro-inflammatory and angiogenic effects, which promote tumor progression and affect the body’s immune response. The study of the lacrimal fluid proved the imbalance of the local immunity not only of the patient, but also of the paired «healthy eye». Research into cytokines leads to a deeper understanding of the pathophysiology of carcinogenesis and may contribute to the development of targeted therapies for inhibiting tumor growth.
About the Authors
V. V. NeroevRussian Federation
Neroev Vladimir V., MD, Academician of Russian Academy of Science, Professor, Director
Sadovaya-Chernogryazskaya str., 14/19, Moscow, 105062
S. V. Saakyan
Russian Federation
Saakyan Svetlana V., MD, Professor, Head of the Ophthalmo-Oncology and Radiology Department
Sadovaya-Chernogryazskaya str., 14/19, Moscow, 105062
L. A. Katargina
Russian Federation
Katargina Ludmila A., MD, Professor, Head of the Eye Pathology in Children Department, Deputy Director
Sadovaya-Chernogryazskaya str., 14/19, Moscow, 105062
N. V. Balatskaya
Russian Federation
Balatskaya Natalia V., PhD (Biology), Leading Researcher, Head of the Immunology and Virology Department
Sadovaya-Chernogryazskaya str., 14/19, Moscow, 105062
I. G. Kulikova
Russian Federation
Kulikova Irina G., Senior Researcher of the Immunology and Virology Department
Sadovaya-Chernogryazskaya str., 14/19, Moscow, 105062
E. B. Myakoshina
Russian Federation
Myakoshina Elena B., PhD, Researcher of the Ophthalmology and Radiology Department
Sadovaya-Chernogryazskaya str., 14/19, Moscow, 105062
References
1. Saakyan S.V., Balatskaya N.V., Katargina L.A., Kulikova I.G., Myakoshina E.B. Subpopulation profile of peripheral blood lymphocytes in uveal melanoma. Medical immunology = Meditsinskaya immunologiya. 2019;21(4):765–772 (In Russ.). DOI: 10.15789/1563-0625-2019-4-765-772
2. Krichevskaja G.I., Slepova O.S., Saakjan S.V., Mjakoshina E.B. The effect of herpesvirus infections on the level of serum interferon-alpha and interferon-gamma in patients with initial choroidal melanoma. Russian Ophthalmological Journal = Rossiyskiy oftal’mologicheskiy zhurnal. 2014;7(2):28–31 (In Russ.).
3. Simbircev A.S. Cytokines are a new system for regulating the body’s defense reactions. Cytokines and inflammation = Citokiny i vospalenie. 2002;1(1):9–16 (In Russ.).
4. Neroev V.V., Zaytseva O.V., Balatskaya N.V., Lazutova A.A. Local and systemic production of 45 cytokines in complicated proliferative diabetic retinopaty. Medical Immunology (Russia) = Meditsinskaya Immunologiya. 2020;22(2):301–310 (In Russ.). DOI: 10.15789/1563-0625-LAS-1802
5. Egorova E.V., Ioshin I.E., Tolchinskaya A.I., Vlasova T.I. Immunologic methods of prediction in complicated cataract surgery. Ophthalmosurgery = Oftal’mohirurgija. 1997;3:25–32 (In Russ.).
6. Nagarkatti-Gude N., Bronkhorst I.H., van Duinen S.G., Luyten G.P., Jager M.J. Cytokines and chemokines in the vitreous fluid of eyes with uveal melanoma. Invest Ophthalmol Vis Sci. 2012;53:6748–6755. DOI: 10.1167/iovs.12-10123.
7. Franco R., Botti G., Mascolo M., Loquercio G., Liguori G., Ilardi G., Losito S., Mura A.L., Calemma R., Ierano C., Bryce J., D’Alterio C., Scalaet S. CXCR4-CXCL12 and VEGF correlate to uveal melanoma progression. Frontiers in bioscience (Elite edition). 2010;2:13–21. DOI: 10.2741/e60
8. Likhvantseva V.G., Slepova O.S., Brovkina A.F. Kinetics of cytokine series immunoregulative peptids production in patients with different stages of uveal melanoma. Medical Immunology (Russia) = Meditsinskaya immunologiya. 1999;1(3–4):39–40 (In Russ.).
9. Karagodin V.P., Mel’nichenko A.A., Orekhov A.N. Chemokine proteins: a role in carcinogenesis and inflammation. Pathogenesis = Patogenez. 2015;13(4):28–33 (In Russ.).
10. Clinical guidelines “Uveal melanoma”, 2020 (In Russ.). https://oncology-association.ru/files/newclinical-guidelines/uvealnaja_melanoma.pdf
11. Amirjan A.G., Saakjan S.V. Prognosis factors for uveal melanoma. Annales of Ophthalmology = Vestnik oftal’mologii. 2015.1:90–94 (In Russ.). DOI: 10.17116/oftalma2015131190-94
12. Myakoshina E.B., Saakyan S.V. Optical coherence tomography in the diagnosis of initial choroidal melanoma. Annales of Ophthalmology = Vestnik oftal’mologii. 2020;136(1):56–64 (In Russ.). DOI: 10.17116/oftalma202013601156
13. Mantovani A., Allavena P., Sica A., Balkwill F. Cancer-related inflammation. Nature. 2008 Jul 24;454(7203):436–444. DOI: 10.1038/nature07205
14. Trinchieri G. Cancer and inflammation: an old intuition with rapidly evolving new concepts. Annu Rev Immunol. 2012;30:677–706. DOI: 10.1146/annurev-immunol-020711-075008
15. Kaplan R.N., Riba R.D., Zacharoulis S., Bramley A.H., Vincent L., Costa C., Mac-Donald D.D., Jin D.K., Shido K., Kerns S.A., Zhu Z., Hicklin D., Wu Y., Port J.L., Altorki N., Port E.R., Ruggero D., Shmelkov S.V.,Jensen K.K., Rafii S., Lyden D. VEGFR1-positive haematopoietic bone marrow progenitors initiate the premetastatic niche. Nature. 2005;438(7069):820–827. DOI: 10.1038/nature04186.8
16. Nguyen D.X., Bos P.D., Massague J. Metastasis: from dissemination to organ-specific colonization. Nat Rev Cancer. 2009;9(4):274–284. DOI: 10.1038/nrc2622
17. Аronow M.E., Topham A.K., Singh A.D. Uveal Melanoma: 5-Year Update on Incidence, Treatment, and Survival (SEER 1973-2013). Ocul Oncol Pathol. 2018;4(3):145–151. DOI: 10.1159/000480640
18. Dunavoelgyi R., Funk M., Sacu S., Georgopoulos M., Zlabinger G., Zehetmayer M., Schmidt-Erfurth U. Intraocular activation of angiogenic and inflammatory pathways in uveal melanoma. Retina. 2012;32:1373–1384. DOI: 10.1097/IAE.0b013e318239e299
19. Vanky F., Nagy N., Hising C., Sjovall K., Larson B., Klein E. Human ex vivo carcinoma cells produce transforming growth factor beta and thereby can inhibit lymphocyte functions in vitro. Cancer Immunol Immunother. 1997;43:317–323.
20. Cao Y., Cao R., Hedlund E.M. R Regulation of tumor angiogenesis and metastasis by FGF and PDGF signaling pathways. J Mol Med (Berl). 2008;86:785–789. DOI: 10.1007/s00109-008-0337-z
21. Ma D., Neiderkorn J.Y. Role of epidermal growth factor receptor in the metastasis of intraocular melanomas. Invest Ophthalmol Vis Sci. 1998;39:1067–1075.
22. Crosby M.B., Yang H., Gao W., Zhang L., Grossniklaus H.E. Serum vascular endothelial growth factor (VEGF) levels correlate with number and location of micrometastases in a murine model of uveal melanoma. British Journal of Ophthalmology. 2011;95:112–117. DOI: 10.1136/bjo.2010.182402
Review
For citations:
Neroev V.V., Saakyan S.V., Katargina L.A., Balatskaya N.V., Kulikova I.G., Myakoshina E.B. Features of the Composition of Cytokines of Various Biological Effects in Patients with Uveal Melanoma: Local Changes in the Lacrimal Fluid. Part 1. Ophthalmology in Russia. 2022;19(1):156-166. (In Russ.) https://doi.org/10.18008/1816-5095-2022-1-156-166