Moreover, the fraction of PD-L1-positive tumor cells, and not macrophages (Supplementary Fig. 4F), interacting with exhausted CD8 + T-cells was significantly higher in Sig3-positive tumors compared to Sig3 negative (p = 0.004; Mann–Whitney U-test, Fig. 5e), indicating that the exhausted CD8 + T-cells are more frequently surrounded by PD-L1-positive tumor cells in Sig3-positive tumors compared to Sig3-negative tumors. Here, CD8A is linked to neoplasm.