TOX and neoplasm: These genes were defined as the tumor reactive signature (TRS), including co-inhibitory receptors (CTLA4, PDCD1, TIGIT and HAVCR2), reactive markers (CD38 and ENTPD1), effector molecules (NKG7 and PRF1), tumor necrosis factor TNFRSF9 and critical exhaustion-related regulator TOX (Figure 3B).