Indeed, a key role for the hypoxia-inducible transcription factor 1 (HIF-1) in the induction of CTLA-4 and LAG-3 expression on tumor infiltrating CD8+ T cells [11], as well as of programmed cell death ligand-1 (PD-L1) on cancer cells [12] has been demonstrated. Here, CTLA4 is linked to neoplasm.