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The following is a summary of “Pharmacodynamic effect of mTOR inhibition-based immunosuppressive therapy on dendritic cell and natural killer cell subsets after renal transplantation,” published in the April 2025 issue of Clinical and Experimental Immunology by Weber et al. 

mTOR inhibitor therapy after kidney transplantation is monitored only by pharmacokinetics. This may not reflect true pathway inhibition, risking improper immunosuppression. 

Researchers conducted a retrospective study to assess the pharmacodynamic effect of mTOR inhibition on NK and dendritic cell subsets after renal transplantation.  

They used phosphoflow cytometry in a cross-sectional study to assess the extent of mTOR inhibition by measuring p70S6K phosphorylation in peripheral dendritic and NK cell subsets of kidney transplant recipients receiving mTORi+CNI (n=17) or mTORi+MPA (n=9). They included 9 patients with dialysis and 17 healthy volunteers as controls for comparison. 

The results showed that mTOR inhibitor-based therapy significantly reduced p70S6K phosphorylation in CD3^–CD56⁺ natural killer cells compared to healthy controls, while no difference was observed in HLA-DR⁺ Lin- total dendritic cells. Patients on mTORi+CNI showed greater inhibition of p70S6K phosphorylation in HLA-DR⁺ Lin- dendritic cells, CD123⁺CD11c^– plasmacytoid DCs, CD123^– CD11c⁺ myeloid DCs, and CD16^–CD56^bright NK cells than those on mTORi+MPA. However, serum trough levels of mTOR inhibitors did not correlate with p70S6K phosphorylation levels in any of the investigated immune cell subsets. 

Investigators selectively suppressed p70S6K phosphorylation in specific dendritic and NK cell subtypes. They suggested phosphoflow cytometry as a clinically applicable method to understand immune subset-specific effects and tailor mTORi therapy. 

Source: academic.oup.com/cei/advance-article-abstract/doi/10.1093/cei/uxaf026/8120800