scRNA-seq reveals tumor microenvironment remodeling induced by local intervention-based immunotherapy

Laser immunotherapy (LIT) combines local photothermal therapy (PTT), to disrupt tumor homeostasis and release tumor antigens, and an intratumorally administered immunostimulant, N-dihydrogalactochitosan (GC), to induce antitumor immune responses. We performed single-cell RNA sequencing on tumor-infiltrating leukocytes of MMTV-PyMT mouse mammary tumors to determine LIT-induced myeloid and lymphoid compartment remodeling. Analysis of 49,380 single cell transcriptomes from different treatment groups revealed proinflammatory IFNa, IFNg, and TNFa cytokine signaling pathways were enriched in both lymphoid and myeloid cells isolated from LIT-treated tumors. Interestingly, the CD4+ and CD8+ T cells in LIT and GC treated tumors resided in an activated state while immune cells in untreated and PTT-treated tumors remained in a neutral/resting state. Additionally, monocytes recruited into the LIT-treated tumors were driven towards proinflammatory M1-like macrophage phenotypes or monocyte-derived dendritic cells. Our results reveal that LIT prompts immunological remodeling of the tumor microenvironment by initiating broad proinflammatory responses to drive antitumor immunity. Overall design: transcriptional profiling of CTRL, PTT, GC, LIT treated CD45+ tumor infiltrating cells performed by single-cell RNA sequencing