CD274 and neoplasm: The same mechanistic rationale may serve to explain why treatment efficacy decreases with more established, higher-volume tumors at baseline (Fig. 6, moving from 6A to 6C): the more established a tumor, the more substantial the gradual accumulation of immuno-suppressive forces in the TME, and the smaller the window of opportunity for immune activation (through the synergistic mechanisms-of-action of RT + anti-PD-(L)1) to overcome resident immuno-suppressive forces.