Medical Radiology and Radiation Safety. 2026. Vol. 71. № 1
DOI:10.33266/1024-6177-2026-71-1-106-112
T.Yu. Mushkarina1, E.G. Kuzmina1, L.Yu. Grivtsova1, G.V. Afonin1, V.A. Biryukov1,
S.A. Ivanov1, 2, A.D. Kaprin2, 3, 4
Response of Circulating Regulatory T Cells to Chemoradiotherapy
of Lung Cancer and Brachytherapy for Prostate Cancer
1 А.F. Tsyb Medical Radiological Research Centre, Obninsk, Russia
2 Peoples Friendship University of Russia (RUDN University), Moscow, Russia
3 National Medical Research Radiological Centre, Obninsk, Russia
4 Р.A. Hertsen Moscow Oncology Research Institute, Moscow, Russia
Contact person: Т.Yu. Mushkarina, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
ABSTRACT
Purpose: To evaluate the dynamics of circulating regulatory T cells (Treg) and changes in their adenosine-dependent functional suppressor activity during chemoradiotherapy of lung cancer (LC) and brachytherapy for prostate cancer (PC).
Material and methods: The study included 19 patients with LC (38 cytometric peripheral blood tests at three control points of chemoradiotherapy) and 23 patients with PC (66 cytometric tests at four control points of brachytherapy). Two control groups were used in the analysis: the main group (40 practically healthy people, blood donors: 22 women and 18 men) to assess the initial level of Treg cells in LC; and an additional group (14 practically healthy people, blood donors) to study the functional activity of Treg cells in patients with LC and PC. The content of Treg cells in patients at the onset of PC was compared with a subgroup of men in the main control group (n=18). Statistical data processing was performed using the Mann–Whitney U-test (pairwise comparison) and the Kruskal‒Wallis criterion (multiple comparison).
Results: Patients with LC and PC before treatment showed a statistically significant increase in the level of circulating Treg cells compared with control values (p<0.05). Chemoradiotherapy with LC led to a significant decrease in the absolute number of Treg cells (p<0.05), but their relative number did not change significantly (p>0.05), which apparently indicates that this subpopulation of cells is not highly sensitive to treatment compared with other lymphocyte subsets. In contrast to Treg cells, the number of B and NK cells decreased more significantly, T helper cells decreased comparably, and T cytotoxic cells decreased to a lesser extent. PC brachytherapy had no statistically significant effect on the level of Treg cells and other lymphocyte subsets (p>0.05). The level of CD39 expression on Treg cells remained stable during treatment with LC and PC and corresponded to the control values (p>0.05).
Conclusion: The high content of Treg cells after chemoradiotherapy LC and PC brachytherapy indicates the persistence of immunosuppression at the systemic level, which negatively affects the results of treatment. The development of strategies for targeted modulation of Treg cells is necessary to increase the effectiveness of cancer therapy.
Keywords: regulatory T cells, lymphocyte subsets, lung cancer, chemoradiotherapy, prostate cancer, brachytherapy
For citation: Mushkarina TYu, Kuzmina EG, Grivtsova LYu, Afonin GV, Biryukov VA, Ivanov SA, Kaprin AD.Response of Circulating Regulatory T Cells to Chemoradiotherapy of Lung Cancer and Brachytherapy for Prostate Cancer. Medical Radiology and Radiation Safety. 2026;71(1):106–112. (In Russian). DOI:10.33266/1024-6177-2026-71-1-106-112
References
1. Ozerskaya Yu.V., Yusubaliyeva G.M., Zhukova O.A., Zykov K.A., Baklaushev V.P. Lung Cancer Immunotherapy: Status Quo, Problems, and Prospects. Meditsina Ekstremal’nykh Situatsiy = Medicine of Extreme Situations. 2024;26;4:87-97 (In Russ.). Doi: 10.47183/mes.2024-26-4-87-97.
2. Kireyeva T.A., Gumenetskaya Yu.V., Biryukov V.A., Obukhov A.A., Makarova K.S., Strikanova I.A., Dzhabrailova S.O. Prophylactic Irradiation of Pelvic Lymph Nodes in Patients with High-Risk Prostate Cancer Progression. Review. Radiatsiya i Risk (Byulleten’ Natsional’nogo Radiatsionnoepidemiologicheskogo Registra) = Radiation and Risk. 2021;30;4:94-107 (In Russ.). Doi: 10.21870/0131-3878-2021-30-4-94-107.
3. Kozlov V.A. Suppressor Cells – the Basis of Immunopathogenesis of Oncological Diseases. Voprosy Onkologii = Problems in Oncologyю 2016;62;3:390-396 (In Russ.).
4. Sennikov S.V., Khantakova Yu.N. The Role of T-Cell Subpopulations in the Induction of Immunological Tolerance. Immunologiya = Immunology. 2017;38;4:239-244 (In Russ.). Doi: 10.18821/0206-4952-2017-38-4-239-244.
5. Zhulay G.A., Oleynik Ye.K., Shibayev M.I., Semakova P.N., Oleynik V.M. Analysis of the Prognostic Significance of CD39 Ectonucleotide Expression by Peripheral Treg Cells in Patients with Colorectal Cancer. Vestnik Ural’skoy Meditsinskoy Akademicheskoy Nauki = Journal of Ural Medical Academic Science. 2020;17;4:323-332 (In Russ.). Doi: 10.22138/2500-0918-2020-17-4-323-332.
6. Vinod S.K., Hau E. Radiotherapy Treatment for Lung Cancer: Current Status and Future Directions. Respirology. 2020;25;2:61-71. Doi: 10.1111/resp.13870. PMID: 32516852.
7. Shchukina Ye.O., Biryukov V.A., Karyakin O.B., Ivanov S.A. High-Power Brachytherapy in Monomode in Patients with Localized Prostate Cancer. Eksperimental’naya i Klinicheskaya Urologiya = Experimental & Clinical Urology. 2023;16;3:136-145 (In Russ.). Doi: 10.29188/2222-8543-2023-16-3-136-145.
8. Qu Y., Jin S., Zhang A., Zhang B, Shi X., Wang J., Zhao Y. Gamma-Ray Resistance of Regulatory CD4+CD25+Foxp3+ T Cells in Mice. Radiat Res. 2010;173;2:148-57. Doi: 10.1667/RR0978.1. PMID: 20095846.
9. Liu R., Xiong S., Zhang L., Chu Y. Enhancement of Antitumor Immunity by Low-Dose Total Body Irradiationis Associated with Selectively Decreasing the Proportion and Number of T Regulatory Cells. Cell Mol Immunol. 2010;7;2:157-62. Doi: 10.1038/cmi.2009.117. PMID: 20140010.
10. Wang B., Li B., Dai Z., Ren S., Bai M., Wang Z., Li Z., Lin S., Wang Z., Huang N., Yang P., Liu M., Min W., Ma H. Low-Dose Splenic Radiation Inhibits Liver Tumor Development of Rats through Functional Changes in CD4+CD25+Treg Cells. Int J Biochem Cell Biol. 2014;55:98-108. Doi: 10.1016/j.biocel.2014. PMID: 25168696.
11. McKelvey K.J., Hudson A.L., Back M., Eade T., Diakos C.I. Radiation, Inflammation and the Immune Response in Cancer. Mamm Genome. 2018;29;11-12:843-865. Doi: 10.1007/s00335-018-9777-0. PMID: 30178305.
12. Principe D.R., Chiec L., Mohindra N.A., Munshi H.G. Regulatory T-Cells as an Emerging Barrier to Immune Checkpoint Inhibition in Lung Cancer. Front Oncol. 2021;11:684098. Doi: 10.3389/fonc.2021.684098. PMID: 34141625.
13. Popov S.V., Sturov N.V., Vorob’yev N.V., Khaydukov S.V. The Role of T-Regulatory Cells in the Progression of Prostate Cancer. Meditsinskaya Immunologiya = Medical Immunology (Russia). 2019;21;4:587-594 (In Russ.). Doi: 10.15789/1563-0625-2019-4-587-594.
14. Boustani J., Joseph E.L.M., Martin E., Benhmida S., Lecoester B., Tochet F., Mirjolet C., Chevalier C., Thibouw D., Vulquin N., Servagi S., Sun X., Adotévi O. Cisplatin-Based Chemoradiation Decreases Telomerase-Specific CD4 TH1 Response but Increases Immune Suppressive Cells in Peripheral Blood. BMC Immunol. 2021;22;1:38. Doi: 10.1186/s12865-021-00429-5. PMID: 34144673.
15. Dutsch-Wicherek M., Chaberek K., Makarewicz A., Antoni S.I., Witwicki J., Bielecki I., Wicherek Ł. The Analysis of Treg Lymphocyte Blood Percentage Changes in Patients with Head and Neck Cancer during Combined Oncological Treatment: a Preliminary Report. Cent Eur J Immunol. 2020;45;4:409-413. Doi: 10.5114/ceji.2020.103417. PMID: 33658889.
16. Baba J., Watanabe S., Saida Y., Tanaka T., Miyabayashi T., Koshio J., Ichikawa K., Nozaki K., Koya T., Deguchi K., Tan C., Miura S., Tanaka H., Tanaka J., Kagamu H., Yoshizawa H., Nakata K., Narita I. Depletion of Radio-Resistant Regulatory T Cells Enhances Antitumor Immunity during Recovery from Lymphopenia. Blood. 2012;120;12:2417-27. Doi: 10.1182/blood-2012-02-411124. PMID: 22806892.
17. Mougiakakos D., Johansson C.C., Kiessling R. Naturally Occurring Regulatory T Cells Show Reduced Sensitivity Toward Oxidative Stress-Induced Cell Death. Blood. 2009;113;15:3542-5. Doi: 10.1182/blood-2008-09-181040. PMID: 19050306.
18. Yarilin A.A. Immunologiya = Immunology. Textbook. Moscow, GEOTAR-Media Publ., 2010. 752 p. (In Russ.).
19. Schoenhals J.E., Cushman T.R., Barsoumian H.B., Li A., Cadena A.P., Niknam S., Younes A.I., Caetano M.D.S., Cortez M.A., Welsh J.W. Anti-Glucocorticoid-Induced Tumor Necrosis Factor-Related Protein (GITR) Therapy Overcomes Radiation-Induced Treg Immunosuppression and Drives Abscopal Effects. Front Immunol. 2018;9:2170. Doi: 10.3389/fimmu.2018.02170. PMID: 30294332.
PDF (RUS) Full-text article (in Russian)
Conflict of interest. The authors declare no conflict of interest.
Financing. The study had no sponsorship.
Contribution. T.Yu. Mushkarina – conducting research, performing statistical data analysis, drafting the manuscript; E.G. Kuzmina – scientific text editing, research design development, scientific guidance; L.Yu. Grivtsova – scientific text editing; G.V. Afonin – collecting research material; V.A. Biryukov – collecting the material; S.A. Ivanov – development of the research concept; A.D. Kaprin – development of the research concept.
Article received: 20.11.2025. Accepted for publication: 25.12.2025.




