Systemic Nos2 Depletion and Cox inhibition limits TNBC disease progression and alters lymphoid cell spatial orientation and density.

ABSTRACT: Antitumor immune polarization is a key predictor of clinical outcomes to cancer therapy. An emerging concept influencing clinical outcome involves the spatial location of CD8⁺ T cells, within the tumor. Our earlier work demonstrated immunosuppressive effects of NOS2 and COX2 tumor expression. Here, we show that NOS2/COX2 levels influence both the polarization and spatial location of lymphoid cells including CD8⁺ T cells. Importantly, elevated tumor NOS2/COX2 correlated with exclusion of CD8⁺ T cells from the tumor epithelium. In contrast, tumors expressing low NOS2/COX2 had increased CD8⁺ T cell penetration into the tumor epithelium. Consistent with a causative relationship between these observations, pharmacological inhibition of COX2 with indom

SUBMITTER: Somasundaram V 

PROVIDER: S-EPMC9661390 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature