Dendritic Cell-Based Immunotherapy in Lung Cancer

Abstract

Lung cancer remains the leading cause of cancer-related death worldwide. The advent of immune checkpoint inhibitors has led to a paradigm shift in the treatment of metastatic non-small cell and small cell lung cancer. However, despite prolonged overall survival, only a minority of the patients derive clinical benefit from these treatments suggesting that the full anti-tumoral potential of the immune system is not being harnessed yet. One way to overcome this problem is to combine immune checkpoint blockade with different strategies aimed at inducing or restoring cellular immunity in a tumor-specific, robust, and durable way. Owing to their unique capacity to initiate and regulate T cell responses, dendritic cells have been extensively explored as tools for immunotherapy in many tumors, including lung cancer. In this review, we provide an update on the nearly twenty years of experience with dendritic cell-based immunotherapy in lung cancer. We summarize the main results from the early phase trials and give an overview of the future perspectives within this field.

Keywords: cancer vaccine; dendritic cell; immune checkpoint blockade; immunotherapy; lung cancer; tumor antigen.

Figure 1

Generic recipe of classical monocyte-derived dendritic cells (DCs). Monocytes are obtained from the patient’s peripheral blood and cultured with IL-4 and GM-CSF to generate immature DCs. These cells are subsequently exposed to activating factors for maturation and loaded with tumor-associated antigens (TAAs). The antigen-loaded DCs are then cryopreserved and injected back into the patient. Different sources of TAAs can be used and include cancer cell line lysate, whole tumor lysate, tumor-derived peptides, (synthetic) protein antigen(s), mRNA(s) encoding selected tumor antigen(s), autologous whole-tumor-derived mRNA, or antigens packaged within viral vectors.

Figure 2

Key parameters to optimize the success of DC-based immunotherapy. CTLA-4, cytotoxic T lymphocyte-associated antigen 4; DC, dendritic cell; MTD, maximum tolerated dose; PD-1, programmed cell death protein 1; PD-L1, programmed death-ligand 1.