The role of dendritic cells in modulating the anti-tumor T cell response

Dendritic cells (DCs) present in the tumor microenvironment (TME) are crucial in influencing T cell response to cancer, as they are responsible for T cell priming and recruitment at tumor site. DCs, however, can have a dual role being able either to induce anti-tumor T cell responses and tolerance and favor the immune escape. Moreover, tumors can manage to exclude DCs from the TME to elude immune surveillance. In this thesis, I will analyze three articles that demonstrate the dual role of DCs in inducing a pro-tumoral and an anti-tumoral response. It has been demonstrated that DCs may be scarce within pancreatic ductal adenocarcinoma (PDA) TME or when present, a specific subset that induces tolerance predominates. Surprisingly, in both cases the result is a pro-tumoral CD4+ T cell response. Differently, in other cancer types, such as lung adenocarcinoma and kidney cancer, DCs presence is associated with anti-tumoral responses, mediated mainly by CD8+ T cells. In particular, it has been discovered that in kidney, bladder and prostate cancer DCs reside in an intra-tumoral lymphatic structure to sustain CD8+ T cells with stem-like features, leading to greater T cell infiltration and better outcomes. In order to revert dysfunctional T cell responses seen in PDA and reinstate an efficient anti-tumor immune surveillance, different therapeutic approaches have been investigated in PDA mouse models. Both DCs mobilization and targeting of molecules or enzymes expressed by tolerogenic DCs were found to be efficient in fulfilling this aim. These results suggest that further studies on how DCs regulate T cell response against cancer may help in the development of more efficient therapies, aimed at reinstating immune surveillance, either inhibiting tolerogenic DCs or enhancing the presence and function of those DCs that induce anti-tumor T cell responses.