Several features associated with response to treatment are compatible with, albeit not definitive evidence for, a model in which PD-1 blockade may be operating within a limited kinetic window of opportunity to achieve durable clinical benefit (Figure 4): Favorable response usually associates with earlier initiation of treatment, smaller tumor burden, and increased likelihood of emerging neoantigen targets to enable sequential waves of T cell response (such as high mutational burden and microsatellite instability) (reviewed in ref. 12). The gene discussed is PDCD1; the disease is neoplasm.