To determine the mechanism(s) by which nivolumab-induced IL-10 production affects the nivolumab-induced T cell responses, we examined the effect of anti-IL-10 mAb and/or nivolumab on the activation of the PD-1 downstream signaling pathways such as AKT [35,36,37], as well as the IL-10 downstream signaling pathway STAT3 that has been shown to be a critical pathway modulating IL-10 mediated anti-tumor T cell responses [16]. This evidence concerns the gene STAT3 and neoplasm.