Fig. 7: Interplay of cytokine production in the tumor microenvironment leading to NOS2hi/COX2hi tumor expressing regions. | Cell Death & Disease

Fig. 7: Interplay of cytokine production in the tumor microenvironment leading to NOS2hi/COX2hi tumor expressing regions.

From: Interferon-gamma is quintessential for NOS2 and COX2 expression in ER- breast tumors that lead to poor outcome

Fig. 7: Interplay of cytokine production in the tumor microenvironment leading to NOS2hi/COX2hi tumor expressing regions.

The secretion of IFNγ by stroma-restricted CD8+ T cells and IL1β/TNFα secreted by myeloid cells within the tumor microenvironment leads to tumor NOS2/COX2 expression and the development of aggressive cellular niches with increased metastatic potential and promotes immunosuppression. Cellular neighborhoods expressing high tumor NOS2/COX2 then increase IL1α/β, creating a feedforward loop that maintains tumor NOS2/COX2 expression and elevated cytokines, including IL8 and IL-6 as well as the activation of latent TGFβ by NO. These factors conspire to promote immunosuppression, metastasis, and cancer stemness through NOS2-derived NO and COX2-derived PGE2.

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