Pharmacological potentiation of monocyte-derived dendritic cell cancer immunotherapy.

Dendritic cells have been at the forefront of cancer-immunotherapy research for over 2 decades. They elicited that attention by having an unprecedented capacity to mount T cells responses against tumors. However, the clinical use of DC-based vaccination against established malignancies has resulted in limited clinical benefits. Several factors are responsible for limiting the efficacy of DC-based immunotherapy, such as the harmful influence of the tumor microenvironment on DCs activity. New insights into the inner process of DC-mediated T cell activation have supported the development of new strategies that potentiate DCs-based therapies. Herein, we identify signaling cascades that have recently been targeted by small molecules and biologicals to promote the activation of monocyte-derived DCs and decrease their susceptibility to becoming tolerogenic. While Statins can markedly enhance antigen presentation, protein kinase inhibitors can be used to increase the expression of co-receptors and adhesion molecules. STAT3 and IDO can be modulated to limit the production of regulatory factors that work against differentiation and activation. The targeting of multiple pathways simultaneously has also been found to produce synergism and drastically enhance DCs activity. Some of these strategies have recently yielded positive results in clinical settings against established malignancies such as non-small cell lung cancer. The emergence of these approaches opens the door for a new generation of potent dendritic cell-based therapeutics to fight cancer.