Postprandial lipid metabolism durably enhances T cell immunity

  • Nature. 2026 Jun;654(8120):1065-1075. doi: 10.1038/s41586-026-10432-8.
Alok Kumar  1  2 ,  Dayana B Rivadeneira  1  2 ,  Isha Mehta  1  3 ,  Bingxian Xie  1  2 ,  Rachel Cumberland  1  2 ,  Supriya K Joshi  1  2 ,  Jitendra S Kanshana  4 ,  William G Gunn  1  2 ,  Victoria Dean  1  2 ,  Angelina Parise  1  2 ,  Kristin Morder  1 ,  Erica S Myers  5 ,  Steven J Mullett  5  6 ,  Richard T Cattley  1 ,  Stacy L Gelhaus  5  6 ,  Abigail E Overacre-Delgoffe  1 ,  Jishnu Das  1  3 ,  William F Hawse  1 ,  Alison B Kohan  4 ,  Greg M Delgoffe  7  8
Affiliations
  • 1. Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.
  • 2. Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA.
  • 3. Department of Computational & Systems Biology, University of Pittsburgh, Pittsburgh, PA, USA.
  • 4. Division of Endocrinology and Metabolism, Pittsburgh, PA, USA.
  • 5. Health Sciences Mass Spectrometry Core, University of Pittsburgh, Pittsburgh, PA, USA.
  • 6. Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.
  • 7. Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA. [email protected].
  • 8. Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. [email protected].
PMID: 42056521 DOI: 10.1038/s41586-026-10432-8
Abstract

Although intrinsic metabolic pathways have critical roles in T cell function1,2, systemic nutrient availability is in constant flux. Yet, how postprandial metabolism affects T cell fate has been less studied. Here we show that the short-term nutritional state of an individual has marked effects on T cell immunity. Human or murine T cells from fed hosts had higher metabolic capacity than those from fasted hosts, and this increase in capacity persisted after activation and expansion in vitro or in vivo. Triglyceride-rich chylomicrons in serum were drivers of postprandial immunometabolic reprogramming, and chylomicrons primed mTORC1-dependent translation ex vivo and after activation, which markedly enhanced effector function after priming. Human postprandial CAR-T cells manufactured from the same donor showed a therapeutic advantage over T cells collected while individuals were fasted. Thus, postprandial metabolism imparts durable metabolic and functional advantages to T cells, highlighting the importance of considering nutritional status in immunological analysis, vaccination and generation of cellular therapies.

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