Immunogenic clearance combined with programmed cell death protein-1 blockade elicits antitumor effect by promoting the recruitment and expansion of the effector memory-like CD8+ T cell

Inducing immunogenic clearance enhances the phagocytosis of dying cancer cells and activates antigen-presenting cells, facilitating the immune system against cancer. This approach can potentially generate robust systemic antitumor immune responses and increase tumor responsiveness to anti-programmed cell death protein 1 (aPD-1) therapy. However, the precise mechanisms underlying this antitumor response induced by immunogenic clearance remain unclear. We used single cell RNA sequencing (scRNA-seq) to understand the underlying mechanism of the therapeutic strategy of immunogenic clearance. Overall design: Here, we employed a B16F10 murine melanoma model, which is resistant to immune checkpoint blockade (ICB). We administered doxorubicin (Dox), an anthracycline that induces immunogenic cell death, and fasudil, a ROCK inhibitor that enhances phagocytosis, to induce immunogenic clearance. We determined the effect of a novel triple combination therapy (Dox+fasudil and aPD-1) on the tumor microenvironment (TME) using single-cell transcriptome profiling.