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PD-1 and LAG-3 as early prognostic markers in the treatment of patients with chronic lymphocytic leukemia

https://doi.org/10.17650/1818-8346-2023-18-4-156-162

Abstract

Background. Recently, studies have been conducted all over the world to study the role of immune checkpoints in the pathogenesis of chronic lymphocytic leukemia (CLL) and the possibility of their use as prognostic markers. Of greatest interest are PD-1 (programmed cell death-1) and LAG-3 protein (lymphocyte-activation gene 3).

Aim. To study the features of PD-1 (CD279) and LAG-3 (CD223) expression on blood B-cells of CLL patients and the possibility of their use as early markers for predicting the hematological response to therapy.

Materials and methods. The blood of 30 patients with CLL in stage C according to Binet and 20 healthy individuals was studied by 10-color flow cytometry.

Results. In patients with CLL, there were significant differences in the initial lymphocytes level, PD-1 and LAG-3 expression on B-lymphocytes, both with persons in the control group and among themselves with different hematological responses to therapy with rituximab according to the results of minimal residual disease monitoring.

Conclusion. PD-1 and LAG-3 can be used as early markers for predicting the response of CLL patients to therapy. The combined use of initial lymphocytes level and PD-1 and LAG-3 expression on CD19+ blood cells has a greater prognostic value. New data obtained from the study of immune checkpoints PD-1 and LAG-3 may be useful in the development of targeted therapeutic agents.

About the Authors

O. N. Selyutina
National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

Olesya N. Selyutina

63 14th Liniya, Rostov-on-Don 344037



I. B. Lysenko
National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

63 14th Liniya, Rostov-on-Don 344037



N. K. Guskova
National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

63 14th Liniya, Rostov-on-Don 344037



I. А. Novikova
National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

63 14th Liniya, Rostov-on-Don 344037



E. Yu. Zlatnik
National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

63 14th Liniya, Rostov-on-Don 344037



T. F. Pushkareva
National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

63 14th Liniya, Rostov-on-Don 344037



N. V. Nikolaeva
National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

63 14th Liniya, Rostov-on-Don 344037



I. A. Kamaeva
National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

63 14th Liniya, Rostov-on-Don 344037



E. A. Kapuza
National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

63 14th Liniya, Rostov-on-Don 344037



Ya. S. Gaysultanova
National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

63 14th Liniya, Rostov-on-Don 344037



L. Ya. Rozenko
National Medical Research Center of Oncology, Ministry of Health of Russia
Russian Federation

63 14th Liniya, Rostov-on-Don 344037



References

1. Nikitin E.A., Bialik T.E., Zaritskii A.Yu. et al. Chronic lymphocytic leukemia/small lymphocytic lymphoma. Clinical recommendations. Sovremennaya onkologiya = Journal of Modern Oncology 2020;22(3):24–44. (In Russ.). DOI: 10.26442/18151434.2020.3.200385

2. Guskova N.K., Selyutina O.N., Novikova I.A. et al. Morphological and immunophenotypic features of the monoclonal population of B-lymphocytes in chronic lymphocytic leukemia. Yuzhnorossiyskiy onkologicheskiy zhurnal = South-Russian Journal of Oncology 2020;1(3):27–35. (In Russ.). DOI: 10.37748/2687-0533-2020-1-3-3

3. Rodríguez-Vicente A.E., Díaz M.G., Hernández-Rivas J.M. Chronic lymphocytic leukemia: a clinical and molecular heterogenous disease. Cancer Genet 2013;206(3):49–62. DOI: 10.1016/j.cancergen.2013.01.003

4. Eichhorst B., Robak T., Montserrat E. et al. Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2021;32(1):23–33. DOI: 10.1016/j.annonc.2020.09.019

5. Wierda W.G., Rawstron A., Cymbalista F. et al. Measurable residual disease in chronic lymphocytic leukemia: expert review and consensus recommendations. Leukemia 2021;35(11):3059–72. DOI: 10.1038/s41375-021-01241-1

6. Fisher A., Goradia H., Martinez-Calle N. et al. The evolving use of measurable residual disease in chronic lymphocytic leukemia clinical trials. Front Oncol 2023;13:1130617. DOI: 10.3389/fonc.2023.1130617

7. Molica S., Giannarelli D., Montserrat E. Minimal residual disease and survival outcomes in patients with chronic lymphocytic leukemia: a systematic review and meta-analysis. Clin Lymphoma Myeloma Leuk 2019;19(7):423–30. DOI: 10.1016/j.clml.2019.03.014

8. Li J.H., Pang N.N., Zhang Z.H. et al. PD-1/PD-L1 expression and its implications in patients with chronic lymphocytic leukemia. Zhonghua Xue Ye Xue Za Zhi 2017;38(3):198–203. DOI: 10.3760/cma.j.issn.0253-2727.2017.03.005

9. Rusak M., Eljaszewicz A., Bolkun L. et al. Prognostic significance of PD-1 expression on peripheral blood CD4+ T cells in patients with newly diagnosed chronic lymphocytic leukemia. Pol Arch Med Wewn 2015;125(7–8):553–9. DOI: 10.20452/pamw.2967

10. Shapiro M., Herishanu Y., Katz B.Z. et al. Lymphocyte activation gene 3: a novel therapeutic target in chronic lymphocytic leukemia. Haematologica 2017;102(5):874–82. DOI: 10.3324/haematol.2016.148965

11. Selyutina O.N., Lysenko I.B., Guskova N.K. et al. Expression of LAG-3 on B-lymphocytes as a marker for prediction of response to therapy in patients with chronic lymphocytic leukemia. Sibirskiy onkologicheskiy zhurnal = Siberian Journal of Oncology 2023;22(2):34–42. (In Russ.). DOI: 10.21294/1814-4861-2023-22-2-34-42

12. Rawstron A.C., Villamor N., Ritgen M. et al. International standardized approach for fl ow cytometric residual disease monitoring in chronic lymphocytic leukaemia. Leukemia 2007;21(5):956–64. DOI: 10.1038/sj.leu.2404584

13. Kit O.I., Timofeeva S.V., Sitkovskaya A.O. et al. Biobank of the National Medical Research Centre for Oncology as a resource for research in the field of personalized medicine. Sovremennaya onkologiya = Journal of Modern Oncology 2022;24(1):6–11. (In Russ.). DOI: 10.26442/18151434.2022.1.201384

14. Kit O.I., Selyutina O.N., Lysenko I.B. et al. A method for predicting the course of chronic lymphocytic leukemia. Patent for invention 2788816 C1, 01.24.2023. Application No. 2022129922 dated 11.18.2022 (In Russ.).

15. Woo S.R., Turnis M.E., Goldberg M.V. et al. Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res 2012;72(4):917–27. DOI: 10.1158/0008-5472.CAN-11-1620

16. Grosso J.F., Kelleher C.C., Harris T.J. et al. LAG-3 regulates CD8+ T cell accumulation and effector function in murine self- and tumor-tolerance systems. J Clin Invest 2007;117(11):3383–92. DOI: 10.1172/JCI31184

17. He Y., Wang Y., Zhao S. et al. sLAG-3 in non-small-cell lung cancer patients’ serum. Onco Targets Ther 2018;11:4781–4. DOI: 10.2147/OTT.S164178

18. Tabakov D.V., Zabotina T.N., Chanturia N.V. et al. Relationship of GITR, Lag-3 and PD-1 expression with the main indicators of systemic and local immunity in patients with breast cancer. Sovremennaya onkologiya = Journal of Modern Oncology 2021;23(3):457–65. (In Russ.). DOI: 10.26442/18151434.2021.3.200809

19. Wang Q., Zhang J., Tu H. et al. Soluble immune checkpoint-related proteins as predictors of tumor recurrence, survival, and T cell phenotypes in clear cell renal cell carcinoma patients. J Immunother Cancer 2019;7(1):334. DOI: 10.1186/s40425-019-0810-y

20. Wang J., Sanmamed M.F., Datar I. et al. Fibrinogen-like protein 1 is a major immune inhibitory ligand of LAG-3. Cell 2019;176(1–2): 334–47.e12. DOI: 10.1016/j.cell.2018.11.010

21. Chang T.T., Kuchroo V.K., Sharpe A.H. Role of the B7-CD28/ CTLA-4 pathway. Curr Dir Autoimmun 2002;5:113–30. DOI: 10.1159/000060550

22. Thibult M.L., Mamessier E., GertnerDardenne J. et al. PD-1 is a novel regulator of human B-cell activation. Int Immunol 2013;25(2):129–37. DOI: 10.1093/intimm/dxs098

23. Badmazhapova D.S., Galtseva I.V., Zvonkov E.E. et al. Expression features of antigens involved in the formation of immunological synapse in chronic lymphocytic leukemia. Onkogematologiya = Oncohematology 2018;13(1):103–14. (In Russ.). DOI: 10.17650/1818-8346-2018-13-1-103-114


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For citations:


Selyutina O.N., Lysenko I.B., Guskova N.K., Novikova I.А., Zlatnik E.Yu., Pushkareva T.F., Nikolaeva N.V., Kamaeva I.A., Kapuza E.A., Gaysultanova Ya.S., Rozenko L.Ya. PD-1 and LAG-3 as early prognostic markers in the treatment of patients with chronic lymphocytic leukemia. Oncohematology. 2023;18(4):156-162. (In Russ.) https://doi.org/10.17650/1818-8346-2023-18-4-156-162

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ISSN 1818-8346 (Print)
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