Tumor NOS2 and COX2 Spatial Juxtaposition with CD8+ T Cells Promote Metastatic and Cancer Stem Cell Niches that Lead to Poor Outcome in ER- Breast Cancer.
Cancer Res Commun
; 2024 Oct 02.
Article
em En
| MEDLINE
| ID: mdl-39356141
ABSTRACT
Estrogen receptor-negative breast cancer is an aggressive subtype with limited therapeutic options. Elevated nitric oxide synthase (NOS2) and cyclo-oxygenase (COX2) mediates immunosuppression and poor survival in these tumors. Therefore, the influence of tumor NOS2/COX2 on immune architecture was examined in 16 African American and 5 Caucasian ER- tumors. Elevated tumor NOS2/COX2 limited CD8+ T cell infiltration at 5-yr survival. Distinct CD8+/-NOS2+/-COX2+/- phenotypes defining metastatic and cancer stem cell niches, and immune desert regions were identified. These results were supported by an unbiased, unsupervised nonlinear dimensionality-reduction UMAP technique incorporating spatial relations between cells and validated in a separate gene expression cohort using NOS2/CD8 and COX2/CD8 ratios. Additionally, elongated tumor cells were specifically in CD8-NOS2+COX2+ regions, suggesting metastatic hot spots. This work demonstrates predictive power of spatial analyses of CD8/NOS2/COX2 architecture and supports the use of clinically available NOS2/COX2 inhibitors for improved survival in patients with these aggressive tumors.
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MEDLINE
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Ano de publicação:
2024
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Article