Reciprocal interactions between tumor killer dendritic cells and tumor-induced regulatory T lymphocytes

Background
Neuroblastoma is the most common extracranial solid tumor in children. Young patients over 1 year of age with metastatic disease have a poor outcome despite advances in chemoradiotherapy, surgery and stem cell transplantation. Therefore, new challenges for the therapy of pediatric neuroblastoma are becoming apparent.

Immunotherapy, the concept of stimulating the body’s immune system to fight cancer, represents an attractive alternative to overcome the resistance of cancer cells to conventional therapies and to chemotherapeutic drugs. This strategy requires the activation of specialized immune cells such as dendritic cells (DC) and T lymphocytes. DC are the most important cells in the initiation of immune responses. They are capable of educating T lymphocytes to specifically recognize and kill cancer cells.

However, tumors have evolved mechanisms to avoid destruction by the immune system. One of the ways by which cancers protect themselves from an immune attack is by promoting the activity of a group of ymphocytes (called CD4+CD25+ regulatory T cells, Treg) which suppress the function of cancer killing T cells.

Project Goal
We have demonstrated that tumor-induced Treg can also inhibit the ability of DC to organize the immune attack against cancer. In addition to their primary role as "conductors" of the immune response, emerging evidence indicates that DC are also endowed with the capacity to directly kill cancer cells. However, the mechanisms by which DC can actually destroy tumor cells is not yet clear. Additionally, it is not yet known if Treg cells can also suppress this DC toxic activity or if killer DC may counteract Treg immunosuppressive function. Understanding these cell interactions is critical since it would permit ‘tumor killer/tumor antigen presenting’ DC to be exploited as more effective anti-cancer cells in immunotherapeutic protocols to fight neuroblastoma.