Indeed, CD8+ T cells in the tumor periphery showed increased expression of genes belonging to costimulatory pathways, including ICOS, TNFRSF4 (OX40) and TNFRSF9 (4-1BB) (Figure 6—figure supplement 1B, Supplementary file 6), albeit accompanied by high levels of inhibitory receptors PDCD1 (PD-1), LAG3, HAVCR2 (TIM-3), and CTLA4 (Figure 6G). Here, ICOS is linked to neoplasm.