Local immunity features in patients with non-invasive muscular bladder cancer of various degrees of malignance
https://doi.org/10.37748/2686-9039-2022-3-4-6
Abstract
Purpose of the study. To study the features of the local distribution of populations of immune system cells in patients with non-invasive muscular bladder cancer of various degrees of malignancy.
Materials and methods. The study included 51 patients with newly diagnosed non-muscle-invasive bladder cancer (papillary urothelial carcinoma) who received complex treatment and follow-up after 9 months at the oncourological department of the National Medical Research Center of Oncology. Patients were divided into two groups: group 1 – with a tumor of low malignant potential (Low grade – LG), n = 31; group 2 – with a tumor of high malignant potential (High grade – HG), n = 20. After 6–9 months, 24 patients were diagnosed with a relapse of the disease – in 48,4 % in patients of group 1 (n = 15) and in 45 % – in group 2 (n = 9). In cell suspensions obtained from the primary and recurrent tumors, as well as the perifocal zone, the relative number of populations of immunocompetent cells was estimated using flow cytometry. A comparison was made of the content of individual populations of lymphocytes in the tumor tissue, the perifocal zone of primary and recurrent lesions of various degrees of malignancy. Statistical processing was performed using Statistica 13.0.
Results. The development of a recurrent tumor of low malignant potential is accompanied by the involvement of cells of innate immunity (NK- and NKT-lymphocytes) into its microenvironment, which is associated with an imbalance in the number of main cells of adaptive immunity – a fairly pronounced decrease in the tumor of T-lymphocytes of the helper-inductor type was noted with a constant content cytotoxic T-lymphocytes, as well as the multidirectional nature of changes in DP- (decrease) and DN-lymphocytes (increase). A feature of the development of a recurrent tumor of high malignant potential is that it is accompanied by the involvement of innate immunity cells (NK- and NKT-lymphocytes) into its microenvironment, as well as multidirectional changes in DP- (decrease) and DN-lymphocytes (increase).
Conclusion. Studies of the population composition of tumors and their perifocal tissues of NMIBC revealed a number of features that are reflected in the redistribution of cytolytic cells, the formation of immunosuppressive conditions, which are reflected both in the manifestation of the biological properties of tumor cells and in changes in the cellular composition of bladder tissues involved in the process. development and progression of cancer.
About the Authors
A. B. SagakyantsRussian Federation
Aleksandr B. Sagakyants - Cand. Sci. (Biol.), associate professor, head of the laboratory of tumor immunophenotyping,
Rostov-on-Don
SPIN: 7272-1408,
AuthorID: 426904,
ResearcherID: M-8378-2019,
Scopus Author ID: 24329773900
L. I. Belyakova
Russian Federation
Lyubov I. Belyakova - PhD student,
63 14 line str., Rostov-on-Don 344037
SPIN: 3382-8559,
AuthorID: 1080471,
ResearcherID: AAH-7729-2020
A. N. Shevchenko
Alexey N. Shevchenko - Dr. Sci. (Med.), professor, head of the oncourology department,
Rostov-on-Don
SPIN: 2748-2638,
AuthorID: 735424,
ResearcherID: Y-5387-2018,
Scopus Author ID: 57192283096
E. S. Bondarenko
Russian Federation
Elena S. Bondarenko - junior research fellow at the laboratory of tumor immunophenotyping,
Rostov-on-Don
SPIN: 3117-4040,
AuthorID: 865798,
Scopus Author ID: 57200132337
E. Yu. Zlatnik
Russian Federation
Elena Yu. Zlatnik - Dr. Sci. (Med.), professor, chief researcher of laboratory of immunophenotyping of tumors,
Rostov-on-Don
SPIN: 4137-7410,
AuthorID: 327457,
Scopus Author ID: 6603160432
I. A. Novikova
Russian Federation
Inna A. Novikova - Cand. Sci. (Med.), deputy director for science,
Rostov-on-Don
SPIN: 4810-2424,
AuthorID: 726229,
ResearcherID: E-7710-2018,
Scopus Author ID: 7005153343
E. V. Filatova
Russian Federation
Elena V. Filatova - Cand. Sci. (Med.), MD, oncologist, researcher department of oncourology,
Rostov-on-Don
SPIN: 7517-1549,
AuthorID: 794870,
Scopus Author ID: 5719228349
V. K. Hvan
Russian Federation
Victor K. Hvan - Cand. Sci. (Med.), urologist of the oncourology department,
Rostov-on-Don
SPIN: 2761-6281,
AuthorID: 1033644
I. A. Khomutenko
Russian Federation
Irina A. Khomutenko - Cand. Sci. (Med.), oncologist, senior researcher of the department of oncourology,
Rostov-on-Don
SPIN: 5401-5810,
AuthorID: 735408
D. V. Burtsev
Russian Federation
Dmitrii V. Burtsev - Dr. Sci. (Med.), chief physician,
Rostov-on-Don
References
1. Salnikova SV, Slavyanskaya ТА, Sepiashvili RI. Modern approaches to diagnosis and prediction of course of urothelial cancer. RUDN Journal of Medicine. 2018; 22(1):9–21. (In Russ.). https://doi.org/10.22363/2313-0245-2018-22-1-9-21
2. IARC, Cancer Today. Estimated number of new cases in 2020, worldwide, both sexes, all ages. 2021. 2022. Available at: https://gco.iarc.fr/today/online-analysis-table, Accessed: 30.10.2022.
3. EAU Guidelines. Edn. presented at the EAU Annual Congress Amsterdam 2022. ISBN 978-94-92671-16-5
4. Kit OI, Shevchenko AN, Komarova EF, Pakus DI, Maksimov AJu. Effect of conjugation matrix metalloproteinase genes polymorphism and their tissue inhibitors with the activity of extracellular proteolysis basement membrane components at early recurrence in patients with superficial bladder cancer. Ural Medical Journal. 2015; 7(130):73–78. (In Russ.).
5. Belyakova LI, Shevchenko AN, Sagakyants AB, Filatova EV. Markers of bladder cancer: their role and prognostic significance (literature review). Cancer Urology. 2021; 17(2):145–156. (In Russ.). https://doi.org/10.17650/17269776-2021-17-2-145-156
6. Khakimova GG, Tryakin AA, Zabotina TN, Khakimova ShG. Comprehensive assessment of the systemic and local immunity, inflammatory factors and clinical indicators in patients with gastric cancer. Malignant Tumoursis. 2020; 10(4):5–15. (In Russ.). https://doi.org/10.18027/2224-5057-2020-10-4-5-15
7. Sharma P, Shen Y, Wen S, Yamada S, Jungbluth AA, Gnjatic S, Bajorin DF, Reuter VE, Herr H, Old LJ, Sato E. CD8 tumor-infiltrating lymphocytes are predictive of survival in muscle-invasive urothelial carcinoma. Proc Natl Acad Sci U S A. 2007 Mar 6; 104(10):3967–3972. https://doi.org/10.1073/pnas.0611618104
8. Horn T, Laus J, Seitz AK, Maurer T, Schmid SC, Wolf P, et al. The prognostic effect of tumour-infiltrating lymphocytic subpopulations in bladder cancer. World J Urol. 2016 Feb; 34(2):181–187. https://doi.org/10.1007/s00345-015-1615-3
9. Zlatnik EYu, Nepomnyaschaya EM, Novikova IA, Aliev TA, Zakora GI, Selyutina ON, et al. Characteristics of local immunity in patients with soft tissue sarcomas. Modern Problems of Science and Education. 2016; 3:93. (In Russ.). Available at: https://science-education.ru/ru/article/view?id=24621, Accessed 30.10.2022.
10. Chen Y, Sun Z, Wan L, Chen H, Xi T, Jiang Y. Tumor Microenvironment Characterization for Assessment of Recurrence and Survival Outcome in Gastric Cancer to Predict Chemotherapy and Immunotherapy Response. Front Immunol. 2022 Apr 29; 13:890922. https://doi.org/10.3389/fimmu.2022.890922
11. Bohner P, Chevalier MF, Cesson V, Rodrigues-Dias SC, Dartiguenave F, Burruni R, et al. Double Positive CD4+CD8+ T Cells Are Enriched in Urological Cancers and Favor T Helper-2 Polarization. Front Immunol. 2019 Mar 29; 10:622. https://doi.org/10.3389/fimmu.2019.00622
12. Wu Z, Zheng Y, Sheng J, Han Y, Yang Y, Pan H, et al. CD3+CD4-CD8- (Double-Negative) T Cells in Inflammation, Immune Disorders and Cancer. Front Immunol. 2022 Feb 10; 13:816005. https://doi.org/10.3389/fimmu.2022.816005
13. Fang L, Ly D, Wang SS, Lee JB, Kang H, Xu H, et al. Targeting late-stage non-small cell lung cancer with a combination of DNT cellular therapy and PD-1 checkpoint blockade. J Exp Clin Cancer Res. 2019 Mar 11; 38(1):123. https://doi.org/10.1186/s13046-019-1126-y
Supplementary files
Review
For citations:
Sagakyants A.B., Belyakova L.I., Shevchenko A.N., Bondarenko E.S., Zlatnik E.Yu., Novikova I.A., Filatova E.V., Hvan V.K., Khomutenko I.A., Burtsev D.V. Local immunity features in patients with non-invasive muscular bladder cancer of various degrees of malignance. South Russian Journal of Cancer. 2022;3(4):58-66. https://doi.org/10.37748/2686-9039-2022-3-4-6