HMGB1 and neoplasm: By competing with nucleic acids for binding to HMGB-1, TIM-3 reduces the amount of nucleic acids that are delivered to the nucleosome and thus inhibits the innate immune response that tumor-associated nucleic acids trigger [35]; and (4) carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM-1) [46], which serves as a self-ligand on T cells, exerts negative modulation on T cell responses [37, 41].