The identification of osteopontin (OPN) as a ligand for CD44 was made in 1997 [70] and has been implicated in a number of physiological and pathological conditions including metastasis of nasopharyngeal carcinoma [71] and bladder cancer [52], as well as control of CD8+ T cell activation and tumor immune evasion [72]. This evidence concerns the gene SPP1 and neoplasm.