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Effect of amino acid restriction diet (SARD) combined with anti-PD-L1 on gene expression of cecum orthotopic CT26 tumors.

ABSTRACT: Since both endogenous synthesis in tumor cells and bacterial sulfur reduction activities are sources of H2S in colon cancer microenvironment, in addition to using CBS -/+ mice, we also investigated the roles of reducing H2S through adopting a sulfur amino acid restriction diet (SARD) (0.15% methionine and 0% cystine) on immunotherapy (anti-PD-L1) of colon cancer. Tumor bulk sequencing was performed in cecum orthotopic CT26 tumors collected from IgG and anti-PD-L1 treated mice both receiving normal diet and SARD.

ORGANISM(S): Mus musculus

PROVIDER: GSE214622 | GEO | 2022/10/05

REPOSITORIES: GEO

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Effect of amino acid restriction diet (SARD) combined with anti-PD-L1 on gene expression of cecum orthotopic CT26 tumors.

Project description:Effect of amino acid restriction diet (SARD) combined with anti-PD-L1 on gene expression of cecum orthotopic CT26 tumors.

| PRJNA886412 | ENA

RNA sequencing of mouse CT26 knockout Pd-l1 cells rescued with WT or K262Q Pd-l1

Project description:Although membrane-anchored Pd-l1 has been well-studied for its engagement with PD-1 on T cells to evade anti-tumor immunity, whether Pd-l1 regulate oncogenic signaling pathways in tumor cells remains elusive. In this experiment, to further dissect roles of the K262 residue acetylation for Pd-l1 nuclear function, we profiled RNA expression of WT or K262Q mutant mouse Pd-l1 re-expressed in CT26 KO Pd-l1 cells. Methods: Total RNA fromCT26/Vector, CT26/WT or CT26 Pd-l1 KO cells was purified using Qiagen RNeasy mini kit (Qiagen) according to the manufacturer’s instructions. Library preparation and sequenceing analysis were performed by BGI-Hong Kong Co. Ltd. Conclusions: Our study indicates that Pd-l1 acetylation modification may affect its function in nuclear.

2020-06-07 | GSE146557 | GEO

RNA sequencing of PD-L1 knock out human MDA-MB231 cells and mouse CT26 cells

Project description:Although membrane-anchored PD-L1 has been well-studied for its engagement with PD-1 on T cells to evade anti-tumor immunity, whether PD-L1 regulate oncogenic signaling pathways in tumor cells remains elusive. Methods: Total RNA from MDA-MB-231 wild type (WT) , MDA-MB-231 PD-L1 knock-out (KO), CT26 WT or CT26 Pd-l1 KO cells was purified using Qiagen RNeasy mini kit (Qiagen) according to the manufacturer’s instructions. Library preparation and sequenceing analysis were performed at the Molecular Genetics Core facility in Dana-Farber Cancer institute. RNA-seq data was aligned using STAR v2.5.4a. Conclusions: Our study indicates that PD-L1 may regulate genes that are involved in immune response regulating pathways.

2020-06-07 | GSE134510 | GEO

QTL mapping reveals novel genes and mechanisms underlying variations in H2S production during alcoholic fermentation in Saccharomyces cerevisiae

Project description:Saccharomyces cerevisiae’s requirement of reduced sulfur to synthesise methionine and cysteine during alcoholic fermentation, is mainly fulfilled through the sulfur assimilation pathway. S. cerevisiae reduces sulfate into sulfur dioxide (SO2) and sulfide (H2S), whose overproduction is a major issue in winemaking, due to its negative impact on wine aroma. The amount of H2S produced is highly strain-specific and depends as well on the SO2 concentration, often added to the grape must. Applying a Bulk Segregant Analysis to a 96 strain-progeny derived from two strains with different ability to produce H2S, and comparing the allelic frequencies along the genome of pools of segregants producing opposite H2S quantities, we identified two causative regions involved in H2S production in the presence of SO2. A functional genetic analysis allowed the identification of variants in four genes: ZWF1, ZRT2, SNR2 and YLR125W, able to impact H2S formation, involved in functions and pathways until now not associated with sulfur metabolism. This data points that redox status and zinc homeostasis are linked to H2S formation in wine fermentation conditions and provides new insights into the regulation of H2S production during wine fermentation, giving a new vision of the interplay between the sulfur assimilation pathway and cell metabolism. This archive contains the transcriptome data of the result of allelic swp for three genes : ZWF1, ZRT2, YLR125w under fermentation.

2024-11-30 | GSE246311 | GEO

PD-L1 regulation of colonic inflammation and colorectal cancerdevelopment

Project description:PD-L1 acts as an immune checkpoint that inhibits T cell activation and suppresses colonic inflammation. We aimed at determine the cellular and molecular mechanisms underlying PD-L1 function in colon epithelium and colon cancer. scRNA-seq was perform to determine the gene expression profiles in epithelial cells and immune cells in the single-cell level. Tumors were induced in WT and PD-L1 KO mice. Analysis of WT and PD-L1 KO tumors revealed that loss of PD-L1 alters T cells, myeloid cells, B cells, and tumor-associated fibroblast subpopulations. Our finding determines that PD-L1 regulates multiple cellular populations to regulates host immune response and tumor development.

2024-10-01 | GSE246038 | GEO

RNAseq of tumor samples from CT26 syngeneic mouse treated with a PD-L1 and CTLA-4 immunotherapy combination

Project description:The ability to modulate immune-inhibitory pathways using checkpoint blockade antibodies such as PD-1, PD-L1, and CTLA-4 represents a significant breakthrough in cancer therapy in recent years. This has driven interest in identifying small-molecule-immunotherapy combinations to increase the proportion of responses. Murine syngeneic models, which have a functional immune system, represent an essential tool for pre-clinical evaluation of new immunotherapies. However, immune response varies widely between models and the translational relevance of each model is not fully understood, making selection of an appropriate pre-clinical model for drug target validation challenging. Utilizing RNAseq transcriptomic profiling, we have characterised the changes in gene regulatory pathways and immune populations in CT26 mice after treatment with the combination of anti-PD-L1 and anti-CTLA-4 antibodies. At day 7 post tumor implant, the pathways analysis of differentially expressed genes indicated an enrichment for migration of leukocytes in response to inflammation and communication between innate and adaptive immune cells. Similarly, analysis of upstream regulators suggested that lipopolysaccharide, IL-1B, TNF, IFNG, and NFKB1A pathways associated with inflammation were activated. At day 14, pathways related T-helper cell signalling pathways were upregulated. In addition, upstream regulators of the lipopolysaccharide and IFNG pathway, as well STAT1 and IL21 pathway were enriched, indicative of innate and adaptive immune response to inflammation.

2020-04-16 | E-MTAB-7777 | biostudies-arrayexpress

RNA sequencing of mouse CT26 knockout Pd-l1 cells rescued with WT or K262Q Pd-l1

Project description:RNA sequencing of mouse CT26 knockout Pd-l1 cells rescued with WT or K262Q Pd-l1

| PRJNA610855 | ENA

Dual Impacts of Serine/Glycine Free Diet in Enhancing Antitumor Immunity and Promoting Evasion via PD-L1 Lactylation [scTCR]

Project description:The effect of Serine/glycine free diet (-SG diet) on colorectal cancer (CRC) remains unclear, meanwhile PD-1 inhibitors are less effective for most CRC patients with proficient mismatch repair/microsatellite stable (pMMR/MSS) characteristics. Here, we demonstrate that -SG diet inhibits CRC growth and promotes the accumulation of cytotoxic T cells to enhance anti-tumor immunity. Additionally, we also identified the lactylation of PD-L1 in tumor cells as a mechanism of immune evasion during cytotocix-T-cell-mediated anti-tumor responses, and blocking PD-1/PD-L1 signaling pathway is able to rejuvenate the function of CD8+ T cells recruited by -SG diet, indicating the clinical potential of combining -SG diet with immunotherapy. Finally, we conducted a single-arm, phase I study, which suggested -SG diet could be a feasible and safe strategy to regulate systemic immunology. Collectively, our findings highlight the promising therapeutic future of -SG diet for treating solid tumors.

2024-09-16 | GSE276920 | GEO

Dual Impacts of Serine/Glycine Free Diet in Enhancing Antitumor Immunity and Promoting Evasion via PD-L1 Lactylation [scRNA-Seq]

2024-09-16 | GSE276916 | GEO

Gene-expression profiles of PD-L1-affected CD8+ T cells

Project description:Programmed cell death 1 ligand 1 (PD-L1) is known to suppress immune system and to be an unfavorable prognostic factor in ovarian cancer. The purpose of this study was to elucidate the function of PD-L1 in peritoneal dissemination. Tumor cell lysis by CTLs was attenuated when PD-L1 on tumor cells was overexpressed and promoted when it was silenced. PD-L1 overexpression also inhibited gathering and degranulation of CTLs. Gene expression profile of mouse CTLs caused by PD-L1-overexpressing ovarian cancer was related to human CTLs exhaustion. In mouse ovarian cancer dissemination models, depleting PD-L1 expression on tumor cells resulted in inhibited tumor growth in the peritoneal cavity and prolonged survival. Restoring immune function by inhibiting immune-suppressive factors such as PD-L1 may be a promising therapeutic strategy for peritoneal dissemination. Genome-wide transcriptional changes in OT-1 mouse CD8+ T cells that were co-incubated with OVA peptide-loaded ID8 mouse ovarian cancer cell lines. CTLs from 4 mice were devided into 2 groups, and co-incubated with PD-L1-overexpressed ID8 or PD-L1-depleted ID8.

2012-07-09 | E-GEOD-39205 | biostudies-arrayexpress

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