Related Experiment Video

Updated: Jun 23, 2025

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS
08:38

Quantification of the Immunosuppressant Tacrolimus on Dried Blood Spots Using LC-MS/MS

Published on: November 8, 2015

16.9K

Pharmacodynamic Effect of mTOR Inhibition-based Immunosuppressive Therapy on T- and B-cell Subsets After Renal

Xinyi Wei1,2, Sabine Weber1, Decheng Yin1

  • 1Pediatric Gastroenterology and Hepatology, Department of Pediatrics and Adolescent Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.

Transplantation Direct
|June 24, 2024
PubMed
Abstract

Insights

Mammalian target of rapamycin inhibitor (mTORi) therapy efficacy in kidney transplant patients can be assessed by measuring p70S6 kinase phosphorylation in lymphocytes. This phosphoflow cytometry method offers insights into individualized immunosuppression strategies.

Area of Science:

  • Immunology
  • Pharmacology
  • Transplantation Medicine

Background:

  • Current monitoring of mammalian target of rapamycin inhibitor (mTORi) therapy post-kidney transplantation relies solely on pharmacokinetic assessment.
  • This approach may not accurately reflect the actual blockade efficacy of the PI3K-Akt-mTOR pathway, potentially leading to suboptimal immunosuppression (under- or over-immunosuppression).

Purpose of the Study:

  • To evaluate the efficacy of mTOR inhibition in peripheral T- and B-lymphocyte subsets using phosphoflow cytometry.
  • To assess the phosphorylation of p70S6 kinase (p70S6K) as a marker for mTOR pathway blockade in renal transplant recipients.

Main Methods:

  • A cross-sectional study involving renal transplant recipients treated with either mTORi plus calcineurin inhibitors (n=18) or mTORi plus mycophenolic acid (n=9).
  • Phosphoflow cytometry was employed to measure p70S6K phosphorylation in peripheral T- and B-lymphocyte subsets.
  • Dialysis patients (n=9) and healthy volunteers (n=17) served as control groups.

Main Results:

  • mTORi treatment significantly reduced p70S6K phosphorylation in CD4+, CD8+ T cells, and CD19+ B cells compared to healthy controls.
  • Specific lymphocyte subsets, including Th cells, transitional B cells, memory B cells, and naive B cells, showed significant reductions in p70S6K phosphorylation.
  • Regulatory T cells and plasmablasts were not significantly affected; mTORi trough levels did not correlate with p70S6K phosphorylation.

Conclusions:

  • mTORi selectively inhibits p70S6K phosphorylation in specific lymphocyte subtypes.
  • Phosphoflow cytometry assessment of p70S6K phosphorylation provides pharmacodynamic information for individualizing mTORi immunosuppression.
  • This method can help optimize immunosuppressive therapy in kidney transplant recipients.

More Related Videos

Murine Full-thickness Skin Transplantation07:59

Murine Full-thickness Skin Transplantation

Published on: January 2, 2017

20.2K
A Semi-Quantitative Drug Affinity Responsive Target Stability DARTS assay for studying Rapamycin/mTOR interaction00:05

A Semi-Quantitative Drug Affinity Responsive Target Stability DARTS assay for studying Rapamycin/mTOR interaction

Published on: August 27, 2019

16.3K

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.8K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
3.5K
Cell-mediated Immune Responses01:40

Cell-mediated Immune Responses

Overview
68.1K
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
511