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ALPN-202 induces a more potent anti-tumor T cell response in MC38/hPD-L1 tumors than PD-L1 blockade alone

ABSTRACT: ALPN-202 induces a more potent anti-tumor T cell response in MC38/hPD-L1 tumors than PD-L1 blockade alone

PROVIDER: PRJNA676031 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13023900.fastq.gz	Fastqsanger.gz
	SRR13023901.fastq.gz	Fastqsanger.gz
	SRR13023902.fastq.gz	Fastqsanger.gz
	SRR13023903.fastq.gz	Fastqsanger.gz
	SRR13023904.fastq.gz	Fastqsanger.gz

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ALPN-202 induces a more potent anti-tumor T cell response in MC38/hPD-L1 tumors than PD-L1 blockade alone

Project description:Purpose: Use RNA-seq to characterize the anti-tumor immune response induced by ALPN-202 and compare to that of anti-PD-L1 treatment alone. Methods: mRNA was isolated from MC38/hPD-L1 tumors 72 hours after a single dose of ALPN-202 (n=4), anti-PD-L1 mAb (durvalumab) (n=4), or Fc control (n=4). Results: ALPN-202 treatment resulted in elevated expression of multiple T cell, NK cell, myeloid cell genes. Additionally, there was a strong increase in genes commonly associated with a proinflammatory response including cytokines, chemokines and surface markers. Conclusions: ALPN-202 treatment resulted in a strong anti-tumor immune response that was more potent than that generated by blockade of PD-L1 alone.

2022-02-10 | GSE161244 | GEO

Single-cell RNAseq of CD45 positive cells in MC38 tumors - Primary irradiated tumors and secondary non-irradiated tumors - Concurrent treatment with anti-PD-L1

Project description:Primary irradiated MC38 tumors and secondary MC38 non-irradiated tumors. Subcutaneous MC38 tumors in C57BL/6 mice Concurrent treatment with anti-PD-L1.

2023-10-15 | E-MTAB-13389 | biostudies-arrayexpress

Macrophage phenotype in anti-PD-L1 treated MC38 tumors

Project description:Macrophage phenotype in anti-PD-L1 treated MC38 tumors

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The microARN-202 (miR-202) controls female fecundity by regulating oogenesis in medaka

Project description:In fish, female fecundity is tightly linked to the proper completion of oogenesis that takes place in the ovary. These cellular processes have been shown to involve both endocrine and intra-ovarian factors. However, the role of small non-coding miRNAs remains largely unknown. Here, we analyzed the role of miR-202, a miRNA specifically expressed in the vertebrate gonads. We first used fluorescent in situ hybridization to determine the precise cellular expression of miR-202 in the medaka ovary. We then generated a mutant fish line (using CRISPR/Cas9 technology) to determine its role in female fecundity and oogenesis. We performed quantitative image analyses to analyze cellular modifications and a genome-wide transcriptomic approach to analyze gene expression modifications. Our results show that miR-202-5p is predominantly expressed in granulosa cells. In addition, mutant females display a drastically reduced fecundity. Our cellular and molecular analyses of ovaries from mutant females indicate that miR-202 deficiency impairs the early steps of oogenesis/folliculogenesis, which ultimately reduce female fecundity. This provides the first functional evidence that miR-202 is necessary for the female reproductive success, in particular the female fecundity, and shed new light on the regulatory mechanisms that control the early steps of follicular development.

2018-08-27 | GSE111388 | GEO

RNA-seq of parental MC38 and anti-PD-1 resistant MC38 subcutaneous tumors

Project description:MC38 tumors resistant to anti-PD-1 treatment (MC38-resistant) were generated through serial in vivo passaging, and global gene expression analysis was used to compare resistant and parental tumors. MC38 and MC38-resistant tumors exhibited widespread changes in global gene expression.

2021-07-22 | GSE180309 | GEO

Immunopeptidome on MC38 Cell line

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PD-L1 regulates dendritic cell ferroptosis during immunogenic chemotherapy [scRNA-seq]

Project description:Dendritic cells (DCs) express high levels of PD-L1 in the tumor microenvironment and draining lymph nodes. Here, we explore the roles of PD-L1 signaling during immunogenic chemotherapy. DC-conditional PD-L1 knockout mice were inoculated with MC38-OVA tumors and treated with doxorubicin. T cells were isolated from draining lymph node for single cell RNA sequencing.

2024-09-23 | GSE223509 | GEO

Macrophage phenotype in anti-PD-L1 treated MC38 tumors

Project description:Checkpoint inhibitors like anti-PD1/PD-L1 have demonstrated significant therapeutic efficacy in a subset of patients partly through reinvigoration of CD8 T cells. However, their impact on myeloid cells remains largely unknown. Here we report that anti-PD-L1 treatment favorably impacts the phenotype and function of tumor macrophages by polarizing the macrophage compartment towards a more pro-inflammatory phenotype. This phenotype was characterized by a decrease in Arginase-I (ARG1) expression and an increase in iNOS, MHCII, and CD40 expression. Whole-transcriptome profiling further confirmed extensive polarization of both tumor monocytes and macrophages from a suppressive to a pro-inflammatory, immuno-stimulatory phenotype. This polarization was driven mainly through IFNγ and was associated with enhanced T cell activity. Transfer of monocytes into anti-PD-L1-treated tumor-bearing mice led to macrophage differentiation into a more pro-inflammatory phenotype, with an increase in CD8 T cells expressing granzyme B and an increase in the CD8/Treg ratio compared to control-treated mice. While in responsive tumor models anti-PD-L1 treatment remodeled the macrophage compartment with beneficial effects on T cells, both macrophage reprogramming and depletion were needed to maximize anti-PD-L1 responses in a tumor immune contexture with high macrophage burden. Our results demonstrate that anti-PD-L1 treatment can favorably remodel the macrophage compartment in responsive tumor models towards a more pro-inflammatory phenotype, mainly through increased IFNγ levels. They also suggest that directly targeting these cells with reprogramming and depleting agents may further augment the breadth and depth of response to anti-PD-L1 treatment in less responsive or more macrophage-dense tumor microenvironments. The "SAMPLE_ID" sample characteristic is a sample identifier internal to Genentech. The ID of this project in Genentech's ExpressionPlot database is NGS1772.

2019-02-12 | GSE125383 | GEO

Small RNA-seq comparing transcriptome (small RNAs) of spermatozoa from rat fed either a standard-Diet (SD) or a High-Protein-Diet (HPD)

Project description:Gene expression analysis of sperm small RNA obtained from rat fed either a standard (SD) or High Protein Diets (HPD). The aim of the study is to identify differentially expressed small RNA in sperm of SD-fed and HPD-fed males which might be involved in the epigenetic inheritance of glucose sensitivity induced by a High Protein Diet.

2021-05-21 | GSE169157 | GEO

Rhodococcus zopfii strain:HPD-2

Project description:Rhodococcus zopfii strain:HPD-2 Genome sequencing and assembly

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