Inulin prebiotic reinforces host cancer immunosurveillance via (sic)d T cell activation

The gut microbiota is now recognized as a key parameter affecting the host's anti-cancer immunosurveillance and ability to respond to immunotherapy. Therefore, optimal modulation for preventive and therapeutic purposes is very appealing. Diet is one of the most potent modulators of microbiota, and thus nutritional intervention could be exploited to improve host anti-cancer immunity. Here, we show that an inulin-enriched diet, a prebiotic known to promote immunostimulatory bacteria, triggers an enhanced Th1-polarized CD4(+) and CD8(+) alpha beta T cell-mediated anti-tumor response and attenuates tumor growth in three preclinical tumor-bearing mouse models. We highlighted that the inulin-mediated anti-tumor effect relies on the activation of both intestinal and tumor-infiltrating (sic)delta T cells that are indispensable for alpha beta T cell activation and subsequent tumor growth control, in a microbiota-dependent manner. Overall, our data identified these cells as a critical immune subset, mandatory for inulin-mediated anti-tumor immunity in vivo, further supporting and rationalizing the use of such prebiotic approaches, as well as the development of immunotherapies targeting (sic)delta T cells in cancer prevention and immunotherapy.

Automated summary

The gut microbiota plays a crucial role in the host's immune response to cancer, and dietary intervention can improve anti-cancer immunity. In this study, an inulin-enriched diet was found to enhance the anti-tumor response of CD4(+) and CD8(+) αβ T cells and reduce tumor growth in mouse models. The anti-tumor effect of inulin was dependent on the activation of intestinal and tumor-infiltrating (δ) T cells, highlighting their importance in anti-tumor immunity.