Evaluation of quantitative changes in regulatory T cells in peripheral blood of kidney transplant recipients with skin cancer after conversion to mTOR inhibitors.

ABSTRACT

INTRODUCTION: Immunosuppressive therapy, necessary for graft survival, has its clinical consequences with an increased risk of developing malignancies being one of them. It seems that the maintenance of a proper balance between cytotoxic and regulatory activity of the immune system may prevent graft rejection, and with a lower risk of cancer. AIM: To assess the quantitative changes in regulatory T cells (Tregs) in peripheral blood of kidney transplant recipients with post-transplantation skin neoplasm after conversion to mTOR inhibitors (mTORi) and to assess the incidence of secondary skin cancer in that group of patients. MATERIAL AND METHODS: Fourteen patients with post-transplant cutaneous malignancies converted to mTORi were included into the study. The control group consisted of eighteen patients maintained on immunosuppressive regimens without mTORi. The level of Tregs with a phenotype defined as CD4lowCD25high was measured before, and 6 months after, mTORi introduction. RESULTS: In all cases, 6 months after conversion, a significant decrease in the ratio of CD4+CD25+ to CD4lowCD25high from 6.52 to 4.29 was detected (p = 0.035). One patient converted to mTORi developed subsequent skin cancer, while in the control group, subsequent skin cancer was recognized in eight patients. Moreover, introducing mTORi significantly improved progression-free survival in this group of patients (p = 0.016). CONCLUSIONS: Introducing mTORi to the immunosuppressive regimen resulted in an increase in the number of regulatory cells without increasing the incidence of secondary skin cancer in the investigated group of patients.