Project description:Colorectal cancer (CRC) continues to increase globally, thus identification of mechanisms that prevent cancer are sorely needed. The microbiota has emerged as a key driver of CRC pathogenesis; however, little is known regarding how specific microbes might prevent CRC. Using transplantation of the microbiota from individuals with or without CRC into germfree mice, we identified that the microbiota harbored by non-diseased individuals can reduce tumor formation and Bacteroides uniformis was a potentially protective member of the microbiota. Single cell sequencing of CD45+ immune cells within the MC38 tumor shows a change in T and NK cell populations with B. uniformis treatment. T cell deficient mice were still protected from CRC in response to B. uniformis treatment, while NK cell depletion eradicated microbe-mediated protection. B. uniformis is reduced in individuals with CRC and thus our data identify B. uniformis as a microbe enriched in healthy individuals that can reduce tumor formation through enhanced NK cell activity.
Project description:Examination of transcriptional changes associated with diet-induced obesity in tumor-infiltrating CD45+ leukocytes from syngeneic MC38 colorectal tumors.
Project description:To determine differential metabolic gene expression in distinct cell populations from subcutaneous MC38 tumors at baseline and in response to rapamycin, tumors from mice treated with vehicle or rapamycin were harvested, reconstituted to single cell suspensions, and flow sorted into cancer cell (CD45-), tumor-associated macrophage (TAM, CD45+ CD11b+ Ly6G- Ly6C lo F4/80 hi), monocytic myeloid-derived suppressor cell (M-MDSC, CD45+ CD11b+ Ly6G- Ly6C hi), CD8 T cell (CD45+ CD3+ CD8a+), and CD4 T cell (CD45+ CD3+ CD8a-) populations. RNA was extracted and transcripts were quantified by the NanoString nCounter Metabolic Pathways Panel.
Project description:Colorectal cancer (CRC), a malignant tumor worldwide consists of microsatellite instability (MSI) and microsatellite stable (MSS) phenotypes. Although SHP2 is a potential target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing was performed to explore the role of SHP2 in all cell types of tumor microenvironment (TME) from murine MC38 xenografts.
Project description:The purpose of this study was to determine the effect of EZH2 inhibitor (EZH2i) PF-06821497 on CD45+ cells isolated from MC38 tumors at day 17 post implantation. Mice were either treated for 7 days prior to endpoint or 16 days prior to endpoint with the EZH2i or with vehicle control. CD45+ cells were isolated and scRNA-Seq was performed on cells
Project description:Tumor microenvironment and transcriptional analysis of CD45+ leukocytes isolated from syngeneic MC38 tumors from mice fed ketogenic diet or control diet
Project description:To better understand the impact of Ufl1 expression in T cells on regulating tumor microenvironment dynamics, we performed single-cell RNA sequencing on purified CD45+ immune cells from MC38 xenografts harvested from Ufl1 cKO or WT C57BL/6 mice.
Project description:To investigate irradiation-induced gene expression profile changes in the tumor microenvironment with a focus on DNA sensing pathways and CXCL/CXCR2 axis at early time points (3h, 12h, 24h) after irradiation. We then performed gene expression profiling analysis using data obtained from 4 tumor tissue from different mice at each time points and the unirradiated control group in both RM9 and MC38 tumor models.
Project description:Exploration of proteome differences between CD45+ and CD45- cell types in renal cell carcinoma tumors and normal adjacent tissue patient samples.