Dendritic Cells and Coregulatory Signals: Immune Checkpoint Blockade to Stimulate Immunotherapy

This chapter discusses the checkpoint receptors on the surface of T cells, and their ligands. Both the receptors and the ligands represent the primary clinical targets for development of the blocking antibodies as a means of enhancing the antitumor immunity. Tumors actively participate in the modeling of their microenvironment. In most solid tumors, the majority of cells in the tumor mass are not cancer cells, but are non-transformed stromal elements consisting of the vasculature, stromal fibroblasts, and hematopoietic cells. The hematopoietic component includes all the elements of the innate and the adaptive immunity with the capacity to generate potent antitumor immunity. It is therefore critical that these cells are maintained in a quiescent state such that their potent cytotoxic machinery is not unleashed and directed at the cancer cells in their midst. The best-studied oncogenic signaling pathway to down-modulate the destructive immune responses in the tumor microenvironment is the Stat3 pathway. The constitutively activated Stat3 enhances the tumor cell proliferation and prevents apoptosis.