Author's View Why is Drug Discovery In Vivo

Cancer immunotherapy has made substantial progress over the past several years, such that immune-based approaches now provide significant benefit to a sub-set of cancer patients, even in the face of advanced disease.1-5 Thus, the discovery and prioritization of new targets is among the foremost challenges for the cancer immunotherapy field. The immune system represents a mobile army whose soldiers—the myriad of functionally and phenotypically spe-cialized subsets of immune cells—con-tinuously patrol the body for threats to the organism. On their journey, immune cells interact with diverse cell populations in distinct microenvironments. Effector T cells play a central role in antitumor immunity and their effectiveness depends on their complex interactions with both cancer cells and many other cell types in various tissue contexts. These include antigen-presenting cells (APCs) in the tumor-draining lymph nodes, tumor-vas-culature endothelial cells, and inhibitory immune cells, such as tumor-infiltrating myeloid-derived suppressor cells. These complex interactions are difficult to model using in vitro culture systems. Our hypothesis is that this complexity pro-vides many opportunities for therapeutic intervention, in particular for discovery of genes that selectively affect T-cell behavior in defined tissue microenvironments, such as occurs in tumors