Two Bugs a NOD Away from Improving Cancer Therapy Efficacy Romina E. Araya, Romina S. Goldszmid  Immunity  Volume 45, Issue 4, Pages 714-716 (October 2016) DOI: 10.1016/j.immuni.2016.10.007 Copyright © 2016 Terms and Conditions

Figure 1 The Efficacy of Cyclophosphamide Is Modulated by Enterococcus hirae and Barnesiella intestinihomini and Improved under a NOD2 Deficiency Context Following cyclophosphamide (CTX) treatment, E. hirae, a gram-positive bacterium, is able to translocate from the small intestine to secondary lymphoid organs, e.g., lymph nodes and spleen, inducing pTh17 and Th1 responses. B. intestinihomini does not translocate, but instead it accumulates in the colon and induces systemic polyfunctional Th1 and Tc1 responses. In tumor-bearing animals after CTX treatment, E. hirae induces an increase in cytotoxic CD8+ T/Treg cell ratio, while B. intestinihomini promotes the increase of intratumoral IFN-γ-producing γδT cells (left panel). When mice are deficient in NOD2 receptor in intestinal epithelial cells (right panel), E. hirae and B. intestinihomini induce epithelial cell death. This barrier dysfunction results in increased translocation of E. hirae from the small intestine and higher accumulation of B. intestinihomini in the colon. Thus, exacerbating the bioactivity of both bacteria and leading to enhanced systemic bacteria-specific immune responses, as well as increased intratumoral CTL/Treg ratio and IFN-γ-producing γδT cells mediated by E. hirae and B. intestinihomini, respectively. Although it is unclear how bacteria-specific responses contribute to anti-tumor immunity, it results in a potentiated CTX-induced anti-tumor response. Immunity 2016 45, 714-716DOI: (10.1016/j.immuni.2016.10.007) Copyright © 2016 Terms and Conditions