THE ROLE OF IMMUNE CHECKPOINT INHIBITORS IN ANTITUMORAL IMMUNITY
Rubrics: REVIEWS
Abstract and keywords
Abstract (English):
Currently immunotherapy is becoming a fairly effective approach in the fight against various forms of malignant neoplasms. This is due to the discovery and use in clinical practice immune checkpoint inhibitors, which antitumoral effect is associated with blockage the signaling pathways CTLA-4 (cytotoxic T-lymphocyte associated protein 4), PD-1 (programmed cell death protein 1), PD-L1 (programmed cell death ligand 1). The physiological role of immune points is to prevent autoimmune tissue damage by suppressing effectors. How- ever, cancer cells have adapted for using this mechanism to avoid elimination by escape mechanisms from immuno- logical surveillance. This gave impetus to the development of drugs that can inhibit checkpoints, enabling the immune system to destroy tumor cells. Actually, 7 drugs have been registered, which can be divided into three groups according to the mechanism of action: CTLA-4 (pilimumab), PD-1 (nivolumab, pembrolizumab, prolgolimab) and PD-L1 (atezoli- zumab, avelumab, durvalumab) inhibitors. The medicine of the first group inhibits the cellular response at the stage of its activation. The mechanism of action of the second and third groups medicines is aimed at blocking the binding of the PD-1 receptor of lymphocytes and monocytes with PD-L1 ligands and vice versa. The use of immune checkpoint inhibitors can lead to the occurrence of immune-mediated adverse reactions, the nature and frequency of which differ depending on the class of inhibitors. In this regard, timely diagnosis and treatment of complications is the key to the success of anticancer therapy.

Keywords:
antitumor therapy, immune checkpoints, immune checkpoint inhibitors, CTLA-4, PD-1, PD-L1
Text
Publication text (PDF): Read Download
References

1. Shubnikova E. V., Bukatina T. M., Vel'c N. Yu., Kaperko D. A., Kutehova G. V. Ingibitory kontrol'nyh tochek immunnogo otveta: novye riski novogo klassa protivoopuholevyh sredstv. Bezopasnost' i risk farmakoterapii. 2020;8(1):9-22. doi:10.30895/2312-7821- 2020-8-1-9-22.

2. Nasonov E. L. Ingibiciya immunnyh kontrol'nyh tochek i autoimmunitet: revmatologicheskie problemy. Nauchno-prakticheskaya revmatologiya. 2018;56(1):5–9. doi:10.14412/1995-4484-2018-5-9.

3. Thommen D.S., Schumacher T.N. T cell dysfunction in cancer. Cancer Cell. 2018;33(4):547-562. doi:10.1016/j.ccell.2018.03.012.

4. Volkov N. M. Immunoterapiya. Prakticheskaya onkologiya. 2018;19(3):226-235. doi:10.31917/1903226.

5. Sakamuri D., Glitza I.C., Betancourt Cuellar S.L., Subbiah V., Fu S., Tsimberidou A.M., et al. Phase I dose-escalation study of anti-CTLA-4 antibody ipilimumab and lenalidomide in patients with advanced cancers. Mol Cancer Ther. 2018;17(3):671-676. doi:10.1158/1535-7163.

6. Simmons D., Lang E. The most recent oncologic emergency: what emergency physicians need to know about the potential complications of immune checkpoint inhibitors. Cureus. 2017;9(10):e1774. doi:10.7759/ cureus.1774.

7. Lepik K. V. Ingibitory immunnyh kontrol'nyh tochek v terapii limfom. Klinicheskaya onkogematologiya. 2018;11(4):303-312. doi:10.21320/2500-2139- 2018-11-4-303-312.

8. Sayapina M. S. Immunoregulyatornye funkcii ingibitorov PD-1/PD-L1 i razvitie k nim rezistentnosti. Zlokachestvennye opuholi. 2017;(2):94-99. doi:10.18027/2224-5057-2017-2-94-99.

9. Boussiotis V.A. Molecular and biochemical aspects of the PD-1 checkpoint pathway. N Engl J Med. 2016;375(18):1767-1778. doi:10.1056/NEJMra1514296.

10. Bolotina L. V., Kaprin A. D. Immunoonkologiya: novye vozmozhnosti lekarstvennoy terapii solidnyh opuholey. Onkologiya. Zhurnal im. P.A. Gercena. 2017;6(5):74-80. doi:10.17116/onkolog20176574-80.

11. Yuzhakova D. V., Shirmanova M. V., Sergeeva T. F., Zagaynova E.V., Luk'yanov K.A. Immunoterapiya zlokachestvennyh novoobrazovaniy. Sovremennye tehnologii v medicine. 2016;8(1):173-182. doi:10.17691/ stm2016.8.1.23.

12. Novik A. V. Sovremennaya immunoterapiya melanomy kozhi. Effektivnaya farmakoterapiya. 2017;(1):26-31.

13. Yudin D. I., Laktionov K. K., Saranceva K. A., Breder V. V., Reutova E. V., Borisova O. I. Ardzinba. Psevdoprogressirovanie na fone immunoterapii. Medicinskiy sovet. 2019;(10):10-14. doi:10.21518/2079- 701X-2019-10-10-14

14. Schadendorf D., Hodi F.S., Robert C., Weber J.S., Margolin K., Hamid O., et al. Pooled Analysis of Long- Term Survival Data From Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma. J Clin Oncol. 2016;33(17):1889-1894. doi:10.1200/ JCO.2014.56.2736

15. Robert C., Schachter J., Long G.V., Arance A., Grob J.J., Mortier L., et al. Pembrolizumab versus ipilimumab in advanced melanoma. New Engl J Med. 2015;372(26):2521-2532. doi:10.1056/ NEJMoa1503093.

16. Rumyancev A. G., Tyulyandin S. A. Effektivnost' ingibitorov kontrol'nyh tochek immunnogo otveta v lechenii solidnyh opuholey. Prakticheskaya onkologiya. 2016;17(2):74-89.

17. Zhukova N.V., Orlova R.V., Kaledina E.A. i dr. Immunoterapiya metastaticheskoy melanomy vche- ra, segodnya, zavtra. Effektivnaya farmakoterapiya. 2021;17(11):22–28. doi:10.33978/2307-3586-2021-17-11- 22-28.

18. Klinicheskie rekomendacii Ministerstva zdravoohraneniya RF “Melanoma kozhi i slizistyh obolochek”, 2020. Dostupno po: https://melanomapro.ru/uploads/docs/ CR_melanoma_2020_final_ compressed.pdf Ssylka aktivna na 24.06.2021.

19. Stroyakovskiy D. L., Abramov M. E., Demidov L. V. i dr. Prakticheskie rekomendacii po lekarstvennomu lecheniyu melanomy kozhi. Zlokachestvennye opuholi: Prakticheskie rekomendacii Rossiyskogo obschestva klinicheskoy onkologii. 2020;10(3s2):266-281. doi:10.18027 / 2224-5057-2020-10-3s2-16.

20. Mann J.E. Atezolizumab (Tecentriq®). Oncology Times. 2017;39(4):31. doi:10.1097/01. cot.0000513325.52233.f1

21. Baxi S., Yang A., Gennarelli R.L., Khan N., Wang Z., Boyce L., Korenstein D. Immune-related adverse events for anti-PD-1 and anti-PD-L1 drugs: systematic review and meta-analysis. BMJ. 2018;(360):k793. doi:10.1136/bmj. k793.

22. Martins F., Sofiya L., Sykiotis G.P., Lamine F., Maillard M., Fraga M., Shabafrouz K., Ribi C., Cairoli A., Guex-Crosier Y., Kuntzer T., Michielin O., Peters S., Coukos G., Spertini F., Thompson J.A., Obeid M. Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance. Nat Rev Clin Oncol. 2019;16(9):563-580. doi:10.1038/s41571-019-0218-0.

Login or Create
* Forgot password?