Compartment-specific PPARδ activity controls the outcome of cancer–immune cell competition and immunotherapy efficacy
T cells sensitize immunotherapy-resistant microsatellite stable metastatic colorectal cancer to checkpoint blockade in mice, and pharmacological or genetic PPARδ activation enhances human chimeric antigen receptor T cell function. These findings identify compartment-specific PPARδ activity as a targetable driver of immune cell fitness that can be harnessed to improve outcomes in immunotherapy-resistant tumors.
Authors
- Jill Habel
- Peter M.K. Westcott (ORCID: https://orcid.org/0000-0001-9436-4857)
- Semir Beyaz (ORCID: https://orcid.org/0000-0003-4730-4012)
- Laura Herrero (ORCID: https://orcid.org/0000-0003-4244-4673)
- John Erby Wilkinson (ORCID: https://orcid.org/0000-0001-9174-8556)
- David E. Rivadeneira
- Saar I. Gill (ORCID: https://orcid.org/0000-0001-7946-7778)
- Nils Wellhausen (ORCID: https://orcid.org/0000-0001-8955-7582)
- Nathalie Y.R. Agar (ORCID: https://orcid.org/0000-0003-3149-3146)
- Charlie Chung (ORCID: https://orcid.org/0000-0003-1566-9498)
- Vinay Mandati (ORCID: https://orcid.org/0000-0001-6560-5033)
- Philip Moresco (ORCID: https://orcid.org/0000-0003-4020-959X)
- Ilgin Ergin (ORCID: https://orcid.org/0000-0002-0007-6502)
- Vyom Shah (ORCID: https://orcid.org/0000-0001-6874-5285)
- Samuel Edward Weinberg (ORCID: https://orcid.org/0000-0002-9532-7051)
- Paul Bunk (ORCID: https://orcid.org/0000-0003-3564-7165)
- Julia Rose Bonney
- Sarah Shao (ORCID: https://orcid.org/0009-0004-4432-4098)
- Lokesh B. S. S. Kumar
- Rachel Rubino
- Timothy Maher
Institutions
- Northwestern University (US)
- Brigham and Women's Hospital (US)
- Harvard University (US)
- Cold Spring Harbor Laboratory (US)
- University of Michigan (US)
- Instituto de Salud Carlos III (ES)
- Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition (ES)
- Donald & Barbara Zucker School of Medicine at Hofstra/Northwell (US)
- Parker Institute for Cancer Immunotherapy (US)
- Dana-Farber Cancer Institute (US)
- Huntington Hospital (US)
- Institut de Biomedicina de la Universitat de Barcelona
- Rutgers New Jersey Medical School (US)
- Stony Brook University (US)
- Universitat de Barcelona (ES)
- University of Pennsylvania (US)
Publication Details
- Journal
- Nature Immunology
- Published
- 2026-10-14
- DOI
- https://doi.org/10.1038/s41590-026-02685-2
- Primary Topic
- Peroxisome Proliferator-Activated Receptors
- Type
- article
- Field-Weighted Citation Impact
- 0.00