Project description:Regulatory T (Treg) cells are crucial for immune homeostasis but they also contribute to tumor immune evasion by promoting a suppressive tumor microenvironment (TME). Mice with Treg cell-restricted Neuropilin 1 deficiency show tumor resistance while maintaining peripheral immune homeostasis, thereby providing a controlled system to interrogate the impact of intratumoral Treg cells on the TME. Using this and other genetic models, we showed that Treg cells shaped the transcriptional landscape across multiple tumor-infiltrating immune cell types. Treg cells suppressed CD8+ T cell secretion of interferon- (IFN), which would otherwise block the activation of sterol regulatory element-binding protein 1 (SREBP1)-mediated fatty acid synthesis in immunosuppressive (M2-like) tumor-associated macrophages (TAMs). Thus, Treg cells indirectly but selectively sustained M2-like TAM metabolic fitness, mitochondrial integrity and survival. SREBP1 inhibition augmented the efficacy of immune checkpoint blockade, suggesting that targeting Treg cells or their modulation of lipid metabolism in M2-like TAMs could improve cancer immunotherapy. Microarray gene expression assay was performed to interogate the impact of fragile (Nrp1–/–) Tregs on the gloabal transcriptome oftumor immune infiltrates (CD45+ cells) at various time points over the course of tumor growth.
Project description:To gain a global understanding of the impact of TREM1 silencing, we analyzed the CD45+ tumor infiltrating cells (TICs) of B16F10 tumor-bearing Trem1+/+ and Trem1-/- mice. Utilizing the 10x Genomics Chromium Platform, we analyzed approximately 5390 cells per sample with a coverage rate of 15493 genes per cell.
Project description:Tumor cells and the anatomical location determine the composition and functionality of the non-malignant tumor microenvironment (TME). To determine the influence of the anatomical location, we have compared the transcriptome of CD45+ tumor-infiltrating immune cells isolated from intra- and extra-cranial tumors, respectively. The same tumor cell line was used to generate both tumor models.
Project description:Gene expression profiling of tumor-infiltrating CD45+CD8+ cells and CD45- tumor cells of tumor bearing mice treated with metformin or anti-PD-1 Ab or both