The microenvironment is critical to the stimulation of aneffective T-cell-mediated antitumor immune response. Presentation of the antigen () to T cells by antigen-presenting cells (APCs) must include theengagement of costimulatory molecules such as B7 (▼) on the APC with CD28(Y) on the T cell. Detection of antigen in the absence of this signalcan result in tolerance. Release of cytokines including interleukin (IL)-12,granulocyte-macrophage colony-stimulating factor (GM-CSF) (by APCs), IL-2 andinterferon (IFN)γ (by T cells) stimulate a strong cellular immuneresponse, whereas local production of IL-10 or transforming growth factor(TGF)-β blunts T cell responsiveness. Finally, for cytotoxic T lymphocytes(CTLs) to be able to recognize their targets, the tumor cells have functionalmajor histocompatibility complex class I tumor antigen presentation ).