Insufficient costimulation of TIL can occur through several routes: senescent T cells infiltrating tumors can lose CD28 expression (25), tumors do not express high levels of costimulatory ligands (26), the tumor microenvironment lacks APCs that effectively activate antitumor immunity (27, 28), and multiple cell types in the tumor microenvironment express inhibitory ligands that suppress TIL activity and antagonize costimulatory signals (29). This evidence concerns the gene CD28 and neoplasm.