Immunotherapeutic advances in gastrointestinal malignancies

Elimination—(1) Apoptotic tumor cells release antigens which are collected by Dendritic cells, (2) Dendritic cells present antigen to CD4？+？T cells in lymph node, which leads to the activation of cytotoxic CD8？+？T cells and B cells, (3) B cells release antibodies; CD8？+？cells release and Perforin/Granzyme, resulting in tumor destruction. Equilibrium—Immune system keeps the tumor in a state of dormancy. Anti-tumor cytokines (IL-12, IFN-γ, TNF-α) and cytotoxic action is countered by pro-tumorigenic/anergy-inducing molecules (IL-10, IL-23, PD-L1) from the tumor. Alteration of genetic pathways within tumor cells also generates new variants which can avoid detection. Escape—Tumor variants utilize (1) decreased expression of antigenic cell surface markers, (2) increased expression of T-cell anergy-inducing cell surface markers (PD-L1, CTLA4), as well as (3) TREG inhibition (via PD-1/PD-L1 interaction) of CD8？+？T cells to overpower immune system. Steps (1), (2) and (3) ultimately result in growth, metastasis, angiogenesis and clinical presentatio