Elucidating the role of CD11b+ conventional dendritic cells (cDC2) in the tumor microenvironment and their potential use as tumor vaccine.

In recent years, immunotherapy of cancer has witnessed remarkable successes, relying on the invigoration of anti-tumor T-lymphocyte responses. For example, immunotherapy with T-cell stimulating immune checkpoint blockers has now been approved for the treatment of several tumor types, including melanoma and non-small cell lung carcinoma (NSCLC). However, how and where
anti-tumor T cells are first activated in vivo is still incompletely understood.
Dendritic cells (DC) are specialized antigen-presenting cells present in all tissues, that play a major role in initiating and orchestrating T-cell-mediated immune responses. Importantly, DC isolated from various steady-state and inflamed tissues have been shown to represent a heterogeneous
population consisting of developmentally distinct DC subsets, including cDC1 and cDC2. cDC1 have been suggested to stimulate anti-tumor immunity, but the role of tumor-associated cDC2 is totally unknown, despite the fact that these cells are usually more numerous. In this project, we will fully characterize the molecular profile of mouse and human melanoma- and NSCLC-associated cDC2 via cutting-edge technologies, assess their in vivo role in mouse tumor models and, finally, investigate their potential for therapeutic anti-tumor vaccination.