Comparison of Antitumor Effects of Combinations of Immune Checkpoint Inhibitors With Dendritic Cells Intratumorally Injected into Irradiated Mouse Adenocarcinoma.

Dendritic cells (DCs) are specialized immune cells that play a crucial role in presenting antigens and activating cytotoxic T lymphocytes to combat tumors. The immune checkpoint receptor programmed cell death-1 (PD-1) can bind to its ligand programmed cell death-ligand 1 (PD-L1), which is expressed on the surface of cancer cells. This interaction suppresses T-cell activation and promotes immune tolerance. Radiation therapy can increase the expression of PD-L1 on tumor cells, which can lead to a decrease in the effectiveness of the treatment, and detailed studies are needed to understand the mechanisms. As many patients develop resistance to chemotherapy and radiotherapy-either through lack of response or cancer recurrence-there is a critical need to maximize synergistic effects by selecting combination treatments that offer improved therapeutic efficacy with minimal side effects. In the present study, immature DCs (iDCs) were introduced directly into irradiated tumor sites (referred as IR/iDCs), and immune checkpoint blockades (ICBs) were administered intraperitoneally. We confirmed the antitumor effect of combining IR/iDCs and ICBs by examining tumor growth and mouse survival. The proportion of CD4+ and CD8+ T cells in splenocytes increased in the IR/iDCs-treated groups. Combining IR/iDCs with an anti-PD-L1 antibody led to a significant reduction in distant tumor growth and improved mouse survival rates compared with IR/iDCs alone or IR/iDCs + anti-PD-1 antibody. These findings suggest that integrating radiotherapy, DC-based immunotherapy, and ICB, specifically targeting PD-L1, may be an effective cancer treatment strategy.