CASP8 and neoplasm: CTLA-4 is constitutively expressed in a variety of tumor cell lines, such as breast, colon, kidney, lung, ovarian, and uterine cancers and in melanoma cell lines, and elevated CTLA-4 expression is associated with the induction of apoptosis through sequential activation of caspase-8 and caspase-3 (42), but the exact role and mechanism of CTLA-4 in ICC remain to be fully elucidated.