T11 Target Structure induced modulations of the pro-inflammatory and anti-infammatorycytokine expressions in experimental animals for glioma abrogation

- T11TS treatment triggers downregulation of pro-inflammatory cytokines (TNF-α, IL-8) in glioma milieu.
- T11TS treatment upregulates anti-inflammatory cytokines like IL-4 and IL-10.
- T11TS treatment inhibits of NF-κB expression in glioma associated brain endothelial cells which is suggestive of decreased activation of pro-angiogenic cytokine IL-6 and IL-8 in tumor endothelial cells.
- Collectively, our results indicate that T11TS therapy modulates inflammatory cytokines in glioma microenvironment in favor of angiogenesis inhibition.

Glioma angiogenesis is the result of the interaction between cancer cells with endothelial cells, and the surrounding inflammatory cells. This interaction plays a crucial role in directing the neo-formation of blood vessels. In the carcinogenic milieu, inflammatory cytokines secreted from inflammatory cells affect endothelial cell functions that are indispensable for tumor growth and metastatic propagation. TNF-α, referred to as the 'inflammatory switch', has shown its potential as an inflammatory agent by activation of IL-8 and IL-6 through NF-κB mediated pathway. Therefore, inhibitors of angiogenesis appear to be promising therapeutic agents for advanced gliomas. Previous studies from our lab showed that T11TS, a membrane glycoprotein, has antiangiogenic and antineoplastic activities in experimental animals and human samples. The present experimental study was designed to evaluate the effect of T11TS therapy on inflammatory cytokine expression of TNF-α, IL-8, IL-6 and their downstream associated molecule NF-κB in vivo. Our results revealed that T11TS therapy induced downregulation of TNF-α, IL-8, IL-6, and NF-κB confirmed by FACS assay and ELISA. In situ-immunofluorescence results hint that T11TS has the efficacy to stop the inflammation related to angiogenesis. Moreover, upregulation of IL-4 and IL-10 in microglia after T11TS therapy helps in complete abrogation of glioma inflammation and angiogenesis. These effects might contribute to the antineoplastic activity of T11TS.

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