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Antagonistic inflammatory phenotypes dictate tumor fate and response to immune checkpoint blockade (scRNA-seq dataset: SZ11)

ABSTRACT: In this study we searched for primary regulators of cancer-inhibitory inflammation using murine tumors of immune-dependent progressive or regressive fates linked to antagonistic inflammatory tumor microenvironments

ORGANISM(S): Mus musculus

PROVIDER: GSE139046 | GEO | 2020/11/20

REPOSITORIES: GEO

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Antagonistic inflammatory phenotypes dictate tumor fate and response to immune checkpoint blockade (RNA-seq dataset: SZ8)

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Project description:Inflammation can support or restrain cancer progression and the response to therapy. Here, we searched for primary regulators of cancer-inhibitory inflammation through deep profiling of inflammatory tumor microenvironments (TMEs) linked to immune-dependent control in mice. We found that early intratumoral accumulation of interferon gamma (IFN-γ)-producing natural killer (NK) cells induced a profound remodeling of the TME and unleashed cytotoxic T cell (CTL)-mediated tumor eradication. Mechanistically, tumor-derived prostaglandin E2 (PGE2) acted selectively on EP2 and EP4 receptors on NK cells, hampered the TME switch, and enabled immune evasion. Analysis of patient datasets across human cancers revealed distinct inflammatory TME phenotypes resembling those associated with cancer immune control versus escape in mice. This allowed us to generate a gene-expression signature that integrated opposing inflammatory factors and predicted patient survival and response to immune checkpoint blockade. Our findings identify features of the tumor inflammatory milieu associated with immune control of cancer and establish a strategy to predict immunotherapy outcomes.

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Antagonistic inflammatory phenotypes dictate tumor fate and response to immune checkpoint blockade

Project description:Antagonistic inflammatory phenotypes dictate tumor fate and response to immune checkpoint blockade

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Antagonistic inflammatory phenotypes dictate tumor fate and response to immune checkpoint blockade

Project description:This SuperSeries is composed of the SubSeries listed below.

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Antagonistic inflammatory phenotypes dictate tumor fate and response to immune checkpoint blockade (RNA-seq dataset: SZ8)

Project description:Antagonistic inflammatory phenotypes dictate tumor fate and response to immune checkpoint blockade (RNA-seq dataset: SZ8)

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Antagonistic inflammatory phenotypes dictate tumor fate and response to immune checkpoint blockade (scRNA-seq dataset: SZ11)

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Project description:Differences in the selective pressures experienced by males and females are believed to be ubiquitous in dioecious organisms and are expected to result in the evolution of sexually antagonistic alleles, thereby driving the evolution of sexual dimorphism. Negative genetic correlation for fitness between the sexes has been documented, however, the identity, number and location of loci causing this relationship are unknown. Here we show that a large proportion of Drosophila melanogaster transcripts are associated with the interaction between genomic haplotype and gender and that at least 8% of loci in the fly genome are currently evolving under sexually antagonistic selection. We measured gene expression of adult males and females of Drosophila melanogaster from 15 hemiclone lines, showing either high-male/low-female fitness, high-female/lowmale fitness or average fitness in both sexes. Data from four replicates for each sex/line are presented, giving a total of 120 arrays.

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