Induction of CD8 T cell cytotoxicity by fecal bacteria from healthy individuals and colorectal cancer patients.

ABSTRACT

Commensal microbiota modulates the anti-tumor immune response and alters the tumor infiltration of T cells in numerous human malignancies. Moreover, the existence of commensals and microbial metabolites has been directly observed inside numerous epithelial tumors. Their effects on the host immune system, independent of the pre-existing malignancy, are not completely understood. To resolve this issue, we compared immune modulatory roles of the fecal bacteria from healthy individuals and the fecal bacteria from colorectal cancer (CRC) patients. Peripheral blood mononuclear cells that were provided by healthy donors were used as study systems. Overall, fecal bacteria could potently activate the degranulation and cytotoxicity of CD8+ T cells. Interestingly, fecal bacteria from CRC patients in general induced higher degranulation and higher cytotoxicity than fecal bacteria from healthy individuals. These effects were dependent on the presence of antigen-presenting cells, such as monocytes and B cells, as fecal bacteria added directly to isolated CD8+ T cells failed to induce high cytotoxicity. Additionally, fecal bacteria from CRC patients induced stronger upregulation of CD80 and NOS2 expression in monocytes than fecal bacteria from healthy individuals. On the other hand, the viability of CD8+ T cells was significantly reduced with increasing levels of bacterial stimulation. Overall, we demonstrated that fecal bacteria from CRC patients could upregulate degranulation and cytotoxicity of CD8+ T cells in a manner that was dependent on antigen-presenting cells, and was more proinflammatory than fecal bacteria from healthy individuals.