This canine trial was paired with detailed mechanistic studies in murine models which demonstrated that the triple therapy of local RT, intratumoral CpG, and systemic IDO not only reduced intratumoral immune suppression/IDO blockade, but also induced robust systemic anti-tumor effects and tumor regression in five dogs with metastatic melanoma and sarcoma (Fig. 1) [98]. The gene discussed is IDO1; the disease is metastatic melanoma.