Subsequently, to analyze the impact of nintedanib, paclitaxel, PD-L1 therapy and the combinations on advanced metastatic disease in immunocompetent mice, we followed similar procedures to that described for MDA-MB-231/LM2–4, ie. orthotopically implant EMT-6/CDDP cells, surgically resect the primary tumors, and then initiate treatment when overt visceral metastasis is present. The gene discussed is CD274; the disease is metastatic neoplasm.