Pharmacological combination of nivolumab with dendritic cell vaccines in cancer immunotherapy: An overview.

In the last decade, immunotherapy led to a paradigm shift in the treatment of numerous malignancies. Alongside with monoclonal antibodies blocking programmed cell death receptor-1 (PD-1)/PD-L1 and cytotoxic T- lymphocyte antigen 4 (CTLA-4) immune checkpoints, cell-based approaches such as CAR-T cells and dendritic cell (DC) vaccines have strongly contributed to pushing forward this thrilling field. While initial strategies were mainly focused on monotherapeutic regimens, it is now consensual that the combination of immunotherapies tackling multiple cancer hallmarks can result in superior clinical outcomes. Here, we review in depth the pharmacological combination of DC-based vaccines that boost tumour elimination by eliciting and expanding effector immune cells, with the PD-1 inhibitor Nivolumab that allows blocking key tumour immune escape mechanisms. This combination represents an important step in cancer therapy, with a significant enhancement in patient survival in several types of tumours, paving an important way in establishing combinatorial immunotherapeutic strategies as first-line treatments.

Dendritic Cell Vaccines for Cancer Immunotherapy: The Role of Human Conventional Type 1 Dendritic Cells.

Throughout the last decades, dendritic cell (DC)-based anti-tumor vaccines have proven to be a safe therapeutic approach, although with inconsistent clinical results. The functional limitations of ex vivo monocyte-derived dendritic cells (MoDCs) commonly used in these therapies are one of the pointed explanations for their lack of robustness. Therefore, a great effort has been made to identify DC subsets with superior features for the establishment of effective anti-tumor responses and to apply them in therapeutic approaches. Among characterized human DC subpopulations, conventional type 1 DCs (cDC1) have emerged as a highly desirable tool for empowering anti-tumor immunity. This DC subset excels in its capacity to prime antigen-specific cytotoxic T cells and to activate natural killer (NK) and natural killer T (NKT) cells, which are critical factors for an effective anti-tumor immune response. Here, we sought to revise the immunobiology of cDC1 from their ontogeny to their development, regulation and heterogeneity. We also address the role of this functionally thrilling DC subset in anti-tumor immune responses and the most recent efforts to apply it in cancer immunotherapy.