While the blockage of CTLA-4 to enhance the initiating step of tumor-specific T-cell priming occurs in the tdLNs, two sites for αPD-1 action are (1) in the tdLN where PD-1 is upregulated with TCR signaling, and (2) in the TME where PD-L1 expression on tumor cells and macrophages can ligate PD-1 on otherwise cytotoxic CD8+ and CD4+ T-cells (Figure 1). The gene discussed is CD8A; the disease is neoplasm.