Single cell transcriptomics of the tumor immune microenvironment from checkpoint blockade-treated KPC tumors
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ABSTRACT: Single cell transcriptomes of CD45+ cells from KPC tumor subcutaneous allografts, either treated with PD-1+CTLA-4 checkpoint blockade or treatment-naïve.
Project description:VAT-EVs from normal or obese mice, serum EVs from normal or obese mice and KPC cells sorted from allografts of normal mouse VAT-EV- or obese mouse VAT-EV-treated mice
Project description:VAT-EVs from normal or obese mice, serum EVs from normal or obese mice and KPC cells sorted from allografts of normal mouse VAT-EV- or obese mouse VAT-EV-treated mice
Project description:VAT-EVs from normal or obese mice, serum EVs from normal or obese mice and KPC cells sorted from allografts of normal mouse VAT-EV- or obese mouse VAT-EV-treated mice
Project description:Test the efficacy of IKE (imidazole ketone) and 10A3 (5-Ethyl-3-(4-methoxybenzyl)-1,3,5-thiadiazinane-2-thione) on KPC tumors from C57B6 mice. Tumors generated by subcutaneous injection of KPC cells were allowed to reach a size of 80-100 mm3. Mice were randomly assigned to four groups and administered 10A3 (20 mg/kg, intraperitoneal, on days 4, 6, 8, 10, 12, 14, and 16) either alone or in combination with IKE (40 mg/kg, intraperitoneal, on days 4, 8, 12, and 16).
Project description:Our study demonstrated that combined treatment with the EZH2 inhibitor tazemetostat and the KRAS inhibitor RMC-6236 significantly suppressed the growth of both subcutaneous and orthotopic tumors. To investigate changes in the tumor microenvironment following combined EZH2 and KRAS inhibition in pancreatic cancer, mice bearing subcutaneous KPC tumors were treated with vehicle, RMC-6236 alone, or RMC-6236 in combination with tazemetostat. CD45⁺ cells were isolated and subjected to 10× Genomics single-cell RNA sequencing.
Project description:global proteomic analysis of subcutaneous white adipose tissue (sWAT) revealed a marked upregulation of proteins involved in oxidative phosphorylation in both male and female KPC mice relative to controls. We also observed a similar induction of oxidative phosphorylation in non-tumour animals treated with the β3-AR agonist CL-316243 to mimic the physiological induction of WAT browning.
Project description:To characterized the effect of IL-27 on the tumor immune microenvironment in vivo, we selected the subcutaneous tumor-infiltrating CD45+ lymphocytes from tumor in vehicle or recombinant mouse IL-27 treated mice,and performed single-cell RNA sequencing on lymphocytes.
Project description:Recently, Bailey et al (2016, Nature) defined four subtypes of pancreatic cancer that are associated with distinct histopathological characteristics and differential survival, namely, Squamous, Pancreatic Progenitor, Immunogenic, and ADEX (Aberrantly Differentiated Endocrine eXocrine). We set out to assess by RNASeq whether loss of CXCR2 was significantly associated with a specific PDAC subtype. Pancreatic tumors were harvested from KPC or KPC Cxcr2-/- mice at endpoint (n=5 v 5), RNA prepared, and RNASeq analysis carried out. Reads were analysed using the bcbio-nextgen framework (https://bcbio-nextgen.readthedocs.org/en/latest/). After quality control and adaptor trimming, reads were aligned to the mouse genome build (UCSC mouse mm10) using STAR. Counts for known genes were generated using the function featureCounts in the R/Bioconductor package \Rsubread\. The R/Bioconductor package edgeR was used to identify differentially expressed genes.
Project description:To examine the effect of tumor-specific TBK1 loss on the tumor immune microenvironment, we performed scRNA-seq on CD45+ cells from B16 tumors from mice treated with anti-PD-1 compared to mice treated with isotype control (IgG).