GZMA and cancer: For example, in our analysis of human melanomas, the correlation between TGF-β and PRF1 / GZMA expression suggests the presence of active CTLs, while increased expression of various negative immune-regulatory markers (i.e., FOXP3, PDL1, CTLA4, LAG3, TIM3, IDO1) may reflect blunting of this anti-tumor response via compensatory mechanisms to establish a dynamic equilibrium between tumor and host during the evolution of these cancers (Fig 2A) [38,58].