Dendritic Cells: Behind the Scenes of T-Cell Infiltration into the Tumor Microenvironment

SIMPLE SUMMARY: High T-cell infiltration has been associated with improved clinical outcomes in many human solid tumors. However, these cells are not autonomous in their effector function, depending on the interaction with other immune and non-immune cells, as well as soluble factors released into the tumor microenvironment (TME). Identification of the key elements underlying T-cell recruitment within tumors is of fundamental importance to improve the success of immunotherapy strategies. This review summarizes the most recent findings on dendritic cells (DC), a key cellular element that regulates the recruitment of functional tumor-specific CD8(+) T cells, and current strategies that exploit this innate immune cell to improve the efficacy of therapeutic treatments. ABSTRACT: Tumor-infiltrating CD8(+) T cells have been shown to play a crucial role in controlling tumor progression. However, the recruitment and activation of these immune cells at the tumor site are strictly dependent on several factors, including the presence of dendritic cells (DCs), the main orchestrators of the antitumor immune responses. Among the various DC subsets, the role of cDC1s has been demonstrated in several preclinical experimental mouse models. In addition, the high density of tumor-infiltrating cDC1s has been associated with improved survival in many cancer patients. The ability of cDC1s to modulate antitumor activity depends on their interaction with other immune populations, such as NK cells. This evidence has led to the development of new strategies aimed at increasing the abundance and activity of cDC1s in tumors, thus providing attractive new avenues to enhance antitumor immunity for both established and novel anticancer immunotherapies. In this review, we provide an overview of the various subsets of DCs, focusing in particular on the role of cDC1s, their ability to interact with other intratumoral immune cells, and their prognostic significance on solid tumors. Finally, we outline key therapeutic strategies that promote the immunogenic functions of DCs in cancer immunotherapy.