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Review

Targeting the PD-1 pathway in pediatric solid tumors and brain tumors

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Pages 2097-2106 | Published online: 12 Apr 2017

Figures & data

Figure 1 Immune response to tumors.

Notes: (A) Dying tumor cells are taken up by antigen-presenting cells (eg, dendritic cells) and presented to T-cells (commonly in the lymph system) where they then undergo clonal expansion and trafficking into the tumor. (B) Activated cytotoxic T-cells proliferate, participate in generation of inflammatory and toxic cytokines, including fatal secretion of perforin and granzyme; following chronic stimulation checkpoint receptors on the T-cells are bound by their ligands and the T-cell response is terminated. Blocking the PD-1 and/or CTLA4 checkpoints with antibodies leads to activation/reactivation of T-cells so they generate an antitumor response.
Abbreviations: MHC, major histocompatibility complex; PD-1, programmed cell death-1; PD-L1, programmed death-ligand 1.
Figure 1 Immune response to tumors.

Figure 2 Escaping immune surveillance.

Notes: T-cells in the immune system recognize and eliminate immunogenic transformed cells. However, some cells do not express enough neoantigens to be recognized by the immune system, while others express ligands for checkpoint receptors on T-cells to terminate the immune response.
Figure 2 Escaping immune surveillance.

Table 1 Checkpoint inhibitors available in the USA and select inhibitors in advanced studies

Table 2 Review of select biomarker studies and their ability to enrich responding patient populations

Table 3 Ongoing trials of agents targeting the PD-1 or PD-L1 pathway for treatment of pediatric cancer