Helper roles of NK and CD8+ T cells in the induction of tumor immunity. Polarized dendritic cells as cancer vaccines.

The work in our laboratory addresses two interrelated areas of dendritic cell (DC) biology: (1) the role of DCs as mediators of feedback interactions between NK cells, CD8+ and CD4+ T cells; and (2) the possibility to use such feedback and the paradigms derived from anti-viral responses, to promote the induction of therapeutic immunity against cancer. We observed that CD8+ T cells and NK cells, the classical "effector" cells, also play "helper" roles, regulating ability of DCs to induce type-1 immune immunity, critical for fighting tumors and intracellular pathogens. Our work aims to delineate which pathways of NK and CD8+ T cell activation result in their helper activity, and to identify the molecular mechanisms allowing them to induce type-1 polarized DCs (DC1s) with selectively enhanced ability to promote type-1 responses and anti-cancer immunity. The results of these studies allowed us and our colleagues to design phase I/II clinical trials incorporating the paradigms of DC polarization and helper activity of effector cells in cancer immunotherapy.