Analysis of changes in subpopulation of T-regulatory cells CD4+CD25+ in metastatic renal cell carcinoma

Introduction. Treatment with interferon alpha (IFN-α) is a possible therapeutic option in patients with metastatic renal cell carcinoma (mRCC) with favorable and intermediate prognosis. However, in some patients there is a lack of clinical effect despite the activation of the cellular component of anti-tumor immunity. According to various authors the CD4⁺CD25⁺ suppressor cells may suppress antitumor immune response, and their study is of scientific interest. Increasing the number of these cells in the peripheral blood was found at various malignancies. Objective. To study the efficiency and tolerance of IFN-α in patients with mRCC and to examine changes in subpopulation of CD4⁺CD25⁺ T-lymphocytes and their association with the efficiency of the therapy. Materials and methods. Forty-one patients with mRCC received IFN-α in 2011 to 2016. Therapy was performed in the 1^st line in 32 patients and in the 2^nd line in 9 patients. Evaluation of immunological parameters was carried out within 1 week prior to immunotherapy, 2 weeks after the beginning and after 8 weeks in the control examination period. The immunophenotype of lymphocytes was assessed by multi-color flow cytometry using antibodies, including CD3, CD4, CD8, CD16, CD20, CD25 and perforin. Statistical analysis and data processing was performed using STATISTICA program (version 13). Results. The complete effect was achieved in 2 (4.8 %) patients, partial regressions were recorded in 9 (21.9 %) patients, and long (≥6 months) stabilizations of a tumor process were observed in other 19 (46.3 %) patients. The overall rate of disease control (complete + partial regressions + long stabilizations) was 73.1 %. The median time to progression was 8 months (p = 0.03). The baseline count of CD4⁺CD25⁺ T-lymphocytes in patients with an objective response was almost within the donor group (3.5 ± 2.1 %) and amounted to 4.4 ± 3.0 % (p <0.05). The baseline count of this subpopulation of cells was thrice greater in patients with the progressive disease: 12.1 ± 8.0 %. It should be noted a tendency to reduce this count during therapy in the group with clinical effect. Conclusion. The baseline count of subpopulations of CD4⁺CD25⁺ T-lymphocytes in the peripheral blood of patients can be a negative prognostic factor in immunotherapy IFN-α, most likely due to immunoregulatory subpopulations of CD4⁺CD25⁺FOXP3⁺CD-127^bw-T-cells (Treg). It is advisable to further study this subpopulation of T-cells as a potential marker of the effectiveness of immunotherapeutic approaches.

Т-регуляторные клетки, интерферон альфа, метастатический почечно-клеточый рак, T-regulatory cells CD4⁺CD25⁺, interferon alpha, metastatic renal cell carcinoma

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