Project description:Time-course bulk RNAseq and single-cell RNAseq of murine AB1 mesothelioma and Renca renal cancer following immune checkpoint therapy
Project description:The on/off dynamics of IFNβ signalling underlie the therapeutic response to immune checkpoint therapy in cancer, which can be exploited to sway the clinical trajectory in favour of response
Project description:The on/off dynamics of IFNβ signalling underlie the therapeutic response to immune checkpoint therapy in cancer, which can be identified in Ly6C+ monocytes
Project description:Purpose: To compare the gene expression profiles of tumors from complete responders and partial responders to cyclophosphamide chemotherapy. AB1-HA murine mesothelioma tumors were excised one day prior to cyclophosphamide or three or seven days post cyclophosphamide.
Project description:Bulk RNA sequencing data of AB1-HA murine mesothelioma tumors from mice treated with tretinoin, immune checkpoint therapy or the combination of tretinoin+immune checkpoint therapy.
Project description:Purpose: Cancer immunotherapy has shown outstanding results in the past few years. Specifically, antibodies targeting immune checkpoints can prolong survival in some patients with various cancer types. However, most patients do not respond, and it is not fully understood what biological processes determine an effective outcome. This lack of understanding hinders the development of rational combination treatments. Methods: Here, we analysed bulk RNAseq data obtained from pretreatment responding and non-responding tumour samples from mice treated with antibodies against CTLA4 and PD-L1. Results: We found that responsive tumours displayed an inflammatory gene expression signature which was consistent with positive upstream regulation by not only IFNγ/STAT1, but also TLR3 and negative regulation by IL-10. Our results identify a pre-treatment cellular microenvironment and molecular signature associated with benefit from immune checkpoint blockade that can be therapeutically attained to improve treatment efficacy.
Project description:RNA from two murine mesothelioma cell lines (AC29 and AB1) was extracted and hybridized to Affymetrix Microarrays to compare gene expression. Both mesothelioma cell lines were established following intraperitoneal introduction of crocidolite (asbestos) fibers (Davis et al. 1992) in CBA mice (AC29 cell line), and BALB/c mice (AB1).
Project description:Exserohilum turcicum (sexual stage Setosphaeria turcica) is the hemibiotrophic causal agent of northern leaf blight of maize and sorghum. This study aimed to identify the genes involved in host colonization during the biotrophic and necrotrophic phases of infection. It also aimed to identify race-specific differences in gene expression. RNAseq of maize seedlings inoculated with a race 13N or 23N E. turcicum isolate was conducted before inoculation and at 2, 5, 7, and 13 days post-inoculation (dpi). Biological replicates were pooled per time point for each race and sequenced. A bioinformatics pipeline was used to identify candidate effectors, and expression was validated for selected candidates. Fungal biomass was positively correlated with the percentages of E. turcicum reads mapped, which were low at early time points (2-7 dpi) with a significant increase at 13 dpi, indicating a lifestyle switch from biotrophy to necrotrophy between 7 and 13 dpi. AVRHt1 is the putative E. turcicum effector recognized by the maize resistance gene Ht1. Consistent with this, AVRHt1 was expressed in planta by race 23N, but transcripts were absent in race 13N. In addition, specific transposable elements were expressed in 23N only. Genes encoding the virulence-associated peptidases leupeptin-inhibiting protein 1 and fungalysin were expressed in planta. Transcriptional profiles of genes involved in secondary metabolite synthesis or cell wall degradation revealed the importance of these genes during late stages of infection (13 dpi). A total of 346 expressed candidate effectors were identified, including Ecp6 and proteins similar to the secreted in xylem (SIX) effectors common to formae speciales of Fusarium oxysporum, SIX13 and SIX5. Expression profiling of Ecp6 and SIX13-like indicated a peak in expression at 5 and 7 dpi compared to 2 and 13 dpi. Sequencing of SIX13-like from diverse isolates of E. turcicum revealed host-specific polymorphisms that were mostly non-synonymous, resulting in two groups of SIX13-like proteins that corresponded to the maize or sorghum origin of each isolate. This study suggests putative mechanisms whereby E. turcicum causes disease. Identification of the candidate effector SIX13-like is consistent with the infection mode of E. turcicum through the xylem of susceptible hosts.