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PD-1 instructs a tumor-suppressive metabolic program that restricts glycolysis and restrains AP-1 activity in T cell lymphoma

A recent study by Wartewig et al. published in Nature Cancer explores the role of PD-1, an immune checkpoint receptor, in T cell non-Hodgkin lymphomas (T-NHLs). PD-1 is known to be a tumor suppressor in T cells, and its inactivation is associated with poor prognosis in advanced T-NHL cases. However, the specific mechanisms by which PD-1 suppresses T cell malignancy are unclear. The study uses mouse models and patient samples to reveal that PD-1 signaling restricts glycolytic energy and acetyl coenzyme A (CoA) production, inhibiting the growth of T-NHL cells. PD-1 inactivation leads to hyperactivity of activating protein 1 (AP-1) transcription factors, promoting cancer growth. Pharmacological inhibition of a key enzyme, ATP citrate lyase (ACLY), which is activated by PD-1 loss, is toxic to PD-1-deficient T-NHLs. This research sheds light on the role of PD-1 in T-NHL and identifies potential therapeutic targets. The IonOpticks Aurora 25cm column was used to analyze samples in this study.


In this research, the IonOpticks Aurora Ultimate 25cm column was used to enhance sensitivity and expand coverage for proteomic analysis.

Journal Article – September 2023  – Nature Cance

Authors:

Tim Wartewig, Jay Daniels, Miriam Schulz, Erik Hameister, Abhinav Joshi, Joonhee Park, Emma Morrish, Anuroop V. Venkatasubramani, Filippo M. Cernilogar, Frits H. A. van Heijster, Christian Hundshammer, Heike Schneider, Filippos Konstantinidis, Judith V. Gabler, Christine Klement, Henry Kurniawan, Calvin Law, Yujin Lee, Sara Choi, Joan Guitart, Ignasi Forne, Jérôme Giustinani, Markus Müschen, Salvia Jain, David M. Weinstock, Roland Rad, Nicolas Ortonne, Franz Schilling, Gunnar Schotta, Axel Imhof, Dirk Brenner, Jaehyuk Choi & Jürgen Ruland

Title

PD-1 instructs a tumor-suppressive metabolic program that restricts glycolysis and restrains AP-1 activity in T cell lymphoma

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