Targeting the mTOR pathway uncouples the efficacy and toxicity of PD-1 blockade in renal transplantation.

ABSTRACT: Immune checkpoint inhibitor (ICI) use remains a challenge in patients with solid organ allografts as most would undergo rejection. In a melanoma patient in whom programmed-death 1 (PD-1) blockade resulted in organ rejection and colitis, the addition of the mTOR inhibitor sirolimus resulted in ongoing anti-tumor efficacy while promoting allograft tolerance. Strong granzyme B⁺, interferon (IFN)-γ⁺ CD8⁺ cytotoxic T cell and circulating regulatory T (T_reg) cell responses were noted during allograft rejection, along with significant eosinophilia and elevated serum IL-5 and eotaxin levels. Co-treatment with sirolimus abated cytotoxic T cell numbers and eosinophilia, while elevated T_reg cell numbers in the peripheral blood were maintained. In

SUBMITTER: Esfahani K 

PROVIDER: S-EPMC6797722 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature