NOS2 and COX2 impact the spatial landscape of CD8+ T cells in ER-breast cancer, providing novel mechanistic insight that drives tumor progression and poor survival
T cells, and induction of B7H4 and cancer-associated fibroblasts driven by significant tumor hypoxia and necrosis. These three types of immune desserts can coexist with each other and with immune hot regions in the same tumor. The coordinated interplay of NOS2 and COX2 indicates that targeting both these enzymes provides an effective treatment strategy that is supported by ongoing clinical trials demonstrating improved clinical outcomes in patients who have otherwise exhausted treatment options.
Authors
- Lisa A. Ridnour (ORCID: https://orcid.org/0000-0001-9446-8349)
- Stephen M. Hewitt (ORCID: https://orcid.org/0000-0001-8283-1788)
- Erika M. Palmieri (ORCID: https://orcid.org/0000-0002-4237-5324)
- Sharon A. Glynn (ORCID: https://orcid.org/0000-0003-1459-2580)
- Stefan Ambs (ORCID: https://orcid.org/0000-0001-7651-9309)
- David A. Wink (ORCID: https://orcid.org/0000-0002-5652-7480)
- William F. Heinz (ORCID: https://orcid.org/0000-0002-6194-0536)
- Daniel W. McVicar (ORCID: https://orcid.org/0000-0002-1112-5111)
- Xiaoxian Li (ORCID: https://orcid.org/0000-0002-0995-1721)
- Leandro Coutinho
- Robert Y.S. Cheng
- Stephen T.C. Wong
- Stephen K. Anderson
- Jenny C. Chang
- Timothy R. Billiar
- M.Cristina Rangel
- Stephen J. Lockett
Institutions
- Leidos (United States) (US)
- National Institutes of Health (US)
- Universidade de São Paulo (BR)
- East Carolina University (US)
- Ollscoil na Gaillimhe – University of Galway (IE)
- Cornell University (US)
- Methodist Hospital (US)
- Frederick National Laboratory for Cancer Research (US)
- University of Pittsburgh Medical Center (US)
- National Cancer Institute (US)
- Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (BR)
- Center for Cancer Research (US)
Publication Details
- Journal
- Redox Biology
- Published
- 2026-04-27
- DOI
- https://doi.org/10.1016/j.redox.2026.104189
- Primary Topic
- Inflammatory mediators and NSAID effects
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Breast Cancer Research Foundation
- John S. Dunn Foundation
- Frederick National Laboratory for Cancer Research
- Ting Tsung and Wei Fong Chao Family Foundation
- Science Foundation Ireland
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- National Institutes of Health
- European Regional Development Fund
- National Cancer Institute