Clinically meaningful survival benefits of PD-1 & CTLA-4 checkpoint inhibitor therapy have been demonstrated in some cancers, such as melanoma and non-small cell lung cancer, but only in a subset of patients (31–34)While observations from murine studies have demonstrated microbiome-associated factors for responsiveness to treatment, another limitation of murine models is their tendency to be reductionistic in their capacity to explore all potential intersecting variables which influence the cancer-immunity cycle (5–8, 15, 35, 36). The gene discussed is CTLA4; the disease is non-small cell lung carcinoma.