The relationship of GITR, Lag-3 and PD-1 expression with the main indicators of systemic and local immunity in patients with breast cancer
- 作者: Tabakov D.1, Zabotina T.1, Chanturia N.2, Zakharova E.1, Vorotnikov I.1, Selchuk V.2, Sokolovskiy V.3, Petrovsky A.1
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隶属关系:
- Blokhin National Medical Research Center of Oncology
- Yevdokimov Moscow State University of Medicine and Dentistry
- Sechenov First Moscow State Medical University (Sechenov University)
- 期: 卷 23, 编号 3 (2021)
- 页面: 457-465
- 栏目: CLINICAL ONCOLOGY
- URL: https://journals.rcsi.science/1815-1434/article/view/60949
- DOI: https://doi.org/10.26442/18151434.2021.3.200809
- ID: 60949
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Background. To enhance the antitumor immune response, new promising methods of immunotherapy are being developed. They consist in the blockade and activation of immune check-point molecules, in particular, the blockade of the Lag‐3 molecule (lymphocyte-activation gene 3) and the activation of the GITR receptor (Glucocorticoid induced TNF receptor). In the studies of combined use with PD-1 blockers, encouraging results were obtained, which makes the assessment of the expression of Lag-3 and GITR on immunocompetent cells of peripheral blood (PB) and tumor tissue necessary for the personalization of such treatment and understanding of the mechanisms of the antitumor immune response.
Materials and methods. The study included peripheral blood samples and surgical material from 39 breast cancer patients being treated at the Blokhin National Medical Research Center of Oncology. The subpopulation composition and expression of PD-1, Lag-3, and GITR molecules were evaluated by flow cytometry.
Results. The analysis of the main populations of PB lymphocytes showed that in patients with breast cancer, the content of NKT-lymphocytes was increased, and the proportions of lymphocytes expressing CD11b and CD25 markers were increased compared to the donor group. It was revealed that the tumor tissue is dominated by T-cells, an increase in the proportion of which occurs due to a reduced content of NK-lymphocytes and B-lymphocytes. The structure of Tumor-infiltrating lymphocytes (TILs) is dominated by subpopulations with immunosuppressive activity, which is indicated by a decrease in the content of CD11b+, CD25+ and perforin-positive cells, increased expression of Lag-3 and PD-1. For PB and tumor tissue, the average degree of dependence of Lag-3 expression on the content of PD-1+ lymphocytes was shown. There is an increase in the content of immunosuppressive subpopulations with high PD-1 values in PB and TILs. The direct dependence of the number of perforin-containing lymphocytes and CD11b expression on the GITR content in the PB was established, but it is not typical for breast cancer tissue.
Conclusion. Since the blockade of the Lag-3 molecule by monoclonal antibodies can enhance the effect of anti-PD-1 therapy in cancer patients, it is necessary to evaluate the expression and co-expression of these two markers. A high content of GITR-positive lymphocytes in the tumor tissue, on the one hand, and a decrease in the proportion of effector subpopulations of lymphocytes, on the other, indicates the influence of the tumor microenvironment on the functioning of GITR-mediated activation of the immune response. Further investigation of GITR expression and functional activity is required to understand the nature of this contradiction.
作者简介
Dmitrii Tabakov
Blokhin National Medical Research Center of Oncology
编辑信件的主要联系方式.
Email: dtabakov91@mail.ru
ORCID iD: 0000-0002-1509-2206
SPIN 代码: 1233-6671
Scopus 作者 ID: 57195612868
Researcher ID: C-1865-2019
Cand. Sci. (Med.)
俄罗斯联邦, MoscowTatiana Zabotina
Blokhin National Medical Research Center of Oncology
Email: tatzabotina@yandex.ru
ORCID iD: 0000-0001-7631-5699
SPIN 代码: 8628-9705
D. Sci. (Biol.)
俄罗斯联邦, MoscowNaily Chanturia
Yevdokimov Moscow State University of Medicine and Dentistry
Email: naily.chanturia@gmail.com
ORCID iD: 0000-0001-7903-6417
Graduate Student
俄罗斯联邦, MoscowElena Zakharova
Blokhin National Medical Research Center of Oncology
Email: zakharovaen@yandex.ru
ORCID iD: 0000-0003-2790-6673
SPIN 代码: 9334-0459
Cand. Sci. (Med.)
俄罗斯联邦, MoscowIgor Vorotnikov
Blokhin National Medical Research Center of Oncology
Email: i.vorotnikov@mail.ru
D. Sci. (Med.), Prof.
俄罗斯联邦, MoscowVladimir Selchuk
Yevdokimov Moscow State University of Medicine and Dentistry
Email: selvu@gmail.com
SPIN 代码: 6180-5569
D. Sci. (Med.), Prof.
俄罗斯联邦, MoscowVictor Sokolovskiy
Sechenov First Moscow State Medical University (Sechenov University)
Email: sokol.2012.vitya@mail.ru
ORCID iD: 0000-0003-0704-2265
student
俄罗斯联邦, MoscowAlexander Petrovsky
Blokhin National Medical Research Center of Oncology
Email: alexpetrovsky@hotmail.com
ORCID iD: 0000-0002-7514-280X
SPIN 代码: 5441-2747
Cand. Sci. (Med.)
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