Specifically, our previous study [6], showed the changes in cytokines gene expression in NSCLC patients’ derived three-dimensional cultures after treatment with MEK and PD-L1 inhibitors (Fig. 1) with an increase of IFNγ, IL-12, IL-6 and TNFα: although the increase of this group of cytokines is able to create a favorable microenvironment for inflammatory and immune response, on the other side it can enhances feedback signals such as the upregulation of other immune checkpoints that are not dependent from the MEK pathway, such as Ido-1 (Fig. 1). The gene discussed is CD274; the disease is non-small cell lung carcinoma.