Ketogenic diet inhibits tumor growth by enhancing immune response, attenuating immunosuppression, inhibiting angiogenesis and EMT in CT26 colon tumor allografts mouse model

Abstract

Ketogenic diet (KD) has increasingly captured the attention of researchers due to its anti-tumor activity. Here, we found that KD treatment significantly enhanced tumor-reactive immune responses, including increased intratumoral CD8+ and CD4+ T cells and decreased FOXP3+/CD4+ Treg cells. Moreover, KD administration increased the Th1-related cytokines IL-2, IFN-γ, IL-1α and IL-12, while decreased Th2-related cytokines IL-4, IL-13 and COX-2, as well as reduced the expression of PD-L1 and CTLA4. Further evaluation revealed that tumor vascularization decreased dramatically after KD treatment. Furthermore, KD reversed the epithelial-mesenchymal transition (EMT) in microenvironmental by up-regulation of E-cadherin, down-regulation of N-cadherin and vimentin. Additionally, KD decrease the expression of phosphorylated STAT1/STAT1, while promoting the expression of P53, Bax/Bcl-2 and caspase-3 in tumor tissues. Thus, our findings indicate that KD treatment can enhance the anti-tumor immunity and mitigate the tumor immunosuppression in the tumor microenvironment, as well as decrease the tumor vascularization.

Keywords

• Ketogenic diet
• Th1 cell
• Treg cell
• Immunosuppression
• Angiogenesis
• EMT