Harnessing the Microbiome to Enhance Cancer Immunotherapy

Figure 1

Lymphodepletion enhances the antitumor activity of transferred T cells. Left panel: without chemotherapy, natural killer (NK) cells act as cytokine sinks that compete for homeostatic cytokines (IL-7 and IL-15) that otherwise help transferred T cells engraft. Additionally, immune suppressive cells, such as regulatory B and T cells (Breg and Treg, resp.) and myeloid derived suppressor cells (MDSC), abrogate the function of transferred T cells. Right panel: lymphodepleting preparative regimens eliminate cytokine sinks and immune suppressive cells leading to enhanced function of transferred T cells. Furthermore, systemic chemotherapy or irradiation impairs gut homeostasis leading to the translocation of bacteria and by-products including LPS (TLR4 agonist). Immature dendritic cells (DC) are activated via TLR4 signaling, which in turn activate transferred T cells. Transferred T cells preferentially expand following the consumption of homeostatic cytokines produced by mature DCs, resulting in potent antitumor responses in vivo.