The Plasticity of CD4+CD25+FOXP3+CD127low T Cells in Patients with Metastatic Renal Cell Carcinoma in the Course of Interferon-Alpha Immunotherapy

Abstract EN

Aims.

To examine changes in subpopulation of CD4+CD25+Foxp3+CD127low T lymphocytes (Treg) and their association with the efficiency of the IFN-α therapy.

Materials and Methods.

Pts with mRCC who had undergone nephrectomy were treated with IFN-α at a dose of 6 × 10 6 U/day three times a week (n = 18).

An immunophenotypic analysis of lymphocytes in peripheral blood expressing CD4, CD25, CD127, and Foxp3 antigens could be performed in 18 pts before, 2 weeks, and 2 mo after IFN-α therapy and 22 normal volunteers.

Blood samples were collected at baseline and 2 mo after treatment start.

Serum levels of TGF-β1, IL-17A, and Epo were measured by ELISA.

Results.

PR was achieved in 3 (16.6%) pts who received first-line therapy.

Long-lasting SD (≥6 months) was noted in 6 (33.3%) pts.

The median progression free survival (PFS) was 4 mo (95% CI: 2-NE).

The study of the population of Treg indicated that there were no significant differences in the groups depending on the effect (p = 0.71).

In one patient, the reduction of Treg cells was associated with increased TGF-β and IL-17 levels, whereas in other two pts the increase in Treg cells was associated with decreased TGF-β and IL-17 levels.

The endogenous levels of Epo did not show significant correlation with response to IFN-α immunotherapy.

In the patient subgroup with an initial value of MCH > 31 pg, the median PFS was not achieved, but in the subgroup with an initial value of MCH < 31 pg, the median PFS was 2 months (p = 0.032).

Conclusions.

In our study, we have described functional plasticity of Treg cells, which prevents them from being used as a prognostic marker.

The conversion of Treg cells into Th17 can serve as a basis for the development of a new specific immunotherapeutic method in oncology after confirmation in the experiment in vitro.

Given the small dataset, the results will need further validation.