Given that IL-6 inhibitors and recombinant IL-12 have individually shown promise for improving the anti-tumor effects of, respectively, PD-1 and PD-L1 blockade, see for example refs. 31,32, we used the systems biology model to examine the timing of their individual and combined immunomodulatory effects, to ultimately determine the optimal treatment protocol leading to maximal patient response. The gene discussed is CD274; the disease is neoplasm.