Combination of Bremachlorin PDT and Immune Checkpoint Inhibitor Anti-PD-1 Shows Response in Murine Immunological T-cell-High and T-cell-Low PDAC Models.

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most challenging types of cancer with little or no response to immune checkpoint inhibitors (ICI). Photodynamic therapy (PDT) has been shown to ablate tumors and induce an immune response. In our study, we investigated the effect of PDT using the photosensitizer Bremachlorin, in its ability to reduce tumor burden and immunologically sensitize T-cell-high and T-cell-low murine PDAC tumors to the ICIs that blocks PD-1 immune checkpoint. In addition, we monitored the effect on survival and investigated if there was a response in PDT-treated and non-PDT-treated distant tumors. Our results showed that Bremachlorin PDT induces direct tumor killing that increased survival in both "hot" T-cell-high and "cold" T-cell-low PDAC tumors and that it can make T-cell-high tumors more sensitive to ICIs blocking PD-1. We found that T-cell-high tumor-bearing mice had an overall greater response to therapy than did T-cell-low tumor-bearing mice. One mouse with T-cell-high tumors exhibited complete tumor regression in both the treated and nontreated distant tumor 90 days after treatment. These results indicate that combining ICIs with Bremachlorin PDT could be a promising therapeutic intervention for enhancing PDAC's response to therapy.