IMMUNOLOGY2026™ Conference Recordings For Attendees-Metabolic Regulation of Alloimmunity: Inhibition of PKM2 Attenuates T Cell Activation and Prolongs Allograft Survival

Metabolic Regulation of Alloimmunity: Inhibition of PKM2 Attenuates T Cell Activation and Prolongs Allograft Survival

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Video Summary

Daniel Marconi presented research showing that the metabolic enzyme PKM2 is a key driver of T cell activation during transplant rejection. In mouse skin transplant models, PKM2 was upregulated in graft-infiltrating leukocytes, especially T cells. Blocking PKM2 with two inhibitors—chikinin, which targets the tetrameric form, and TEPP-46, which targets the dimeric form—reduced T cell proliferation, interferon-gamma production, and activation in vitro. In vivo, these inhibitors prolonged graft survival, with the combined treatment giving the strongest protection, including in more stringent transplant models. PKM2 inhibition also reduced graft inflammation and altered T cell mitochondrial features, increasing mitochondrial mass and ROS. Similar effects were seen in a humanized transplant model using human PBMCs. Overall, the study suggests PKM2 is a promising metabolic checkpoint for reducing allograft rejection, though toxicity and long-term tolerance remain important questions.

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Date April 17, 2026 5:00 PM - 5:15 PM

Room 102

Session From A to X: Next-Gen Targets & Interventions for Alloimmunity, GVHD, and Xenotransplantation

Speaker Daniel Marconi Mendes

Track Transplantation Immunology (TRAN)

Year 2026

Keywords

PKM2

T cell activation

transplant rejection

allograft survival

metabolic checkpoint

April 17, 2026 5:00 PM - 5:15 PM

102

From A to X: Next-Gen Targets & Interventions for Alloimmunity, GVHD, and Xenotransplantation

Daniel Marconi Mendes

Transplantation Immunology (TRAN)

2026