Sustained NO Production by Engineered Bacteria: A Dual Strategy of Tumor Vasculature Normalization and T-cell Exhaustion Reversal for Robust Immunotherapy

To further illustrate that RAGH+alphaPDL1 remodels the tumor immunosuppressive microenvironment, we performed scRNA-seq on CD45+ cells isolated from MC38 tumors on day 7 after treatment. Unsupervised cluster analysis using the two-dimensional t-distributed stochastic neighbor embedding (t-SNE) algorithm, cell types for these clusters were then identified based on canonical markers, which included B cells, DCs, mast cells, monocytes, macrophages, neutrophils, granulocytes, NK cells, and T cells . Among them, the number of pro-tumor macrophages was significantly decreased, anti-tumor macrophages, NK cells and T cells was significantly increased. More importantly, further analysis of T cells showed a significant increase in memory CD8+ T cells, indicating that RAGH+alphaPDL1 has important application value for long-lasting anti-tumor immunity