The Plasticity of CD4 + CD25 + FOXP3 + CD127 low T Cells in Patients with Metastatic Renal Cell Carcinoma in the Course of Interferon-Alpha Immunotherapy.

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 × 106  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- β 1, 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.