FIG 5.

Hypothesized model of patterns of response and progression to programmed cell death protein 1 (PD-1) blockade. PD-1 blockade is proposed to achieve benefit largely from a systemic, clonal-directed antitumor immune response, which is recruited from the periphery to infiltrate tumors (lavender arrows), consistent with the uniform spatiotemporal pattern of response across metastases seen within a given patient (top right panel). In contrast, patterns of progression can be more mixed, which may reflect the heterogenous and organ-specific properties of the local tumor microenvironment (red dashed circles) that can block or restrain the systemic immune response to PD-1 blockade, and produce mixed progression across metastases within a given patient (bottom right panel).