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Antigen cross-presentation in young tumor-bearing hosts promotes CD8 T cell terminal differentiation [WGBS]

ABSTRACT: Antigen cross-presentation in young tumor-bearing hosts promotes CD8 T cell terminal differentiation [WGBS]

PROVIDER: PRJNA778717 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR16856296_1.fastq.gz	Fastqsanger.gz
	SRR16856296_2.fastq.gz	Fastqsanger.gz
	SRR16856297_1.fastq.gz	Fastqsanger.gz
	SRR16856297_2.fastq.gz	Fastqsanger.gz
	SRR16856298_1.fastq.gz	Fastqsanger.gz

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Antigen cross-presentation in young tumor-bearing hosts promotes CD8 T cell terminal differentiation

Project description:Antigen cross-presentation in young tumor-bearing hosts promotes CD8 T cell terminal differentiation

| PRJNA778706 | ENA

Antigen cross-presentation in young tumor-bearing hosts promotes CD8 T cell terminal differentiation [gene expression]

Project description:Antigen cross-presentation in young tumor-bearing hosts promotes CD8 T cell terminal differentiation [gene expression]

| PRJNA778718 | ENA

Antigen cross-presentation in young tumor-bearing hosts promotes CD8 T cell terminal differentiation [WGBS]

Project description:The immune system undergoes a progressive functional remodeling with age, polarizing the immune responses toward a “killer” or “healer” phenotype. Understanding how the age bias shapes anti-tumor immunity is essential in designing effective immunotherapies. In this manuscript we explore the anti-tumor CD8+ T cell responses generated in young (prepubescent) and adult (pre-senescent) mice. Using an MHCI-deficient, trackable tumor model, we observed that tumor reactive CD8+ T cells that expanded in young tumor-bearing (TB) mice acquired a terminally differentiated phenotype characterized by overexpression of inhibitory receptors and the transcription factor Tox1. Furthermore, tumor infiltrating CD8+ T cells from young tumors yielded a poor cytokine response compared to CD8+ T cells infiltrating adult tumors. Young migratory dendritic cells (migDC) and mononuclear phagocytic cells (MPCs) infiltrating young tumors were more competent in capturing and cross-presenting tumor antigen, leading to enhanced priming of CD8+ T cells in the draining lymph nodes (dLNs), and their subsequent terminal differentiation in the tumors. Notably, single-cell transcriptional profiling of tumor infiltrating MPCs revealed that young MPCs are polarized toward an inflammatory, effector phenotype. Consistent with our observations in young vs adult TB mice, analysis of immune infiltrates from pediatric solid tumors revealed a significant correlation between tumor-infiltrating CD8+ T cells with an exhaustion phenotype and the frequency of PD-L1-expressing phagocytic cells. Collectively, these data indicate that the young microenvironment of an actively developing tissue contributes to the generation of an immune response skewed toward a terminal effector state, thus narrowing the window for immunotherapeutic interventions.

2022-02-28 | GSE188388 | GEO

Antigen cross-presentation in young tumor-bearing hosts promotes CD8 T cell terminal differentiation [gene expression]

2022-02-28 | GSE188387 | GEO

Antigen cross-presentation in young tumor-bearing hosts promotes CD8 T cell terminal differentiation

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

2022-02-28 | GSE188389 | GEO

Antigen cross-presentation in young tumor-bearing hosts promotes CD8<sup>+</sup> T cell terminal differentiation.

Project description:The immune system undergoes a progressive functional remodeling with age. Understanding how age bias shapes antitumor immunity is essential in designing effective immunotherapies, especially for pediatric patients. Here, we explore antitumor CD8+ T cell responses generated in young (prepubescent) and adult (presenescent) mice. Using an MHCI-deficient tumor model, we observed that tumor-reactive CD8+ T cells expanded in young tumor-bearing (TB) mice acquired a terminally differentiated phenotype characterized by overexpression of inhibitory receptors and the transcription factor Tox1. Furthermore, tumor-infiltrating CD8+ T cells from young tumors yielded a poor cytokine response compared with CD8+ T cells infiltrating adult tumors. Young migratory dendritic cells (migDCs) from the draining lymph nodes (dLNs), and mononuclear phagocytic cells (MPCs) infiltrating young tumors, were more competent in capturing and cross-presenting tumor antigen, leading to enhanced priming of CD8+ T cells in dLNs and their subsequent terminal differentiation in the tumors. Single-cell transcriptional profiling of tumor-infiltrating MPCs demonstrated that young MPCs are polarized toward an inflammatory, effector phenotype. Consistent with our observations in young versus adult TB mice, analysis of immune infiltrates from pediatric solid tumors showed a correlation between tumor-infiltrating CD8+ T cells with an exhaustion phenotype and the frequency of PD-L1-expressing monocytes/macrophages. Collectively, these data indicate that a young tissue microenvironment contributes to the generation of an immune response skewed toward a less pliable terminal effector state, thus narrowing the window for immunotherapeutic interventions.

| S-EPMC8990347 | biostudies-literature

Gene profile analysis of sorted Sca1+/cKit- BMCs obtained from young and aged mice bearing tumor or not

Project description:Sca1+/cKit– hematopoietic BMCs of hosts bearing primary tumors promote the growth of distant tumors that form with a myofibroblast-rich, desmoplastic stroma. BMCs from old mice bearing primary tumors lack this ability

2016-07-21 | GSE74120 | GEO

Gene profile analysis of sorted Sca1+/cKit- BMCs obtain from mice bearing instigator, non-instigator and Matrigel

2010-11-27 | GSE25620 | GEO

Gene profile analysis of sorted Sca1+/cKit- BMCs obtain from mice bearing instigator, non-instigator and Matrigel

Project description:Sca1+/cKit– hematopoietic BMCs of hosts bearing instigating tumors (BPLER) promote the growth of responding (HMLER-HR) tumors that form with a myofibroblast-rich, desmoplastic stroma. BMCs from mice bearing Non-instigating tumors lack this ability Sca1+/cKit- BMCs were isolated from mice bearing Matrigel control or size-matched instigating or non-instigating tumors by FACS directly into Trizol reagent (Invitrogen).

2010-11-27 | E-GEOD-25620 | biostudies-arrayexpress

Gene profile analysis of sorted Sca1+/cKit- BMCs obtained from young and aged mice bearing tumor or not

Project description:Sca1+/cKitâ hematopoietic BMCs of hosts bearing primary tumors promote the growth of distant tumors that form with a myofibroblast-rich, desmoplastic stroma. BMCs from old mice bearing primary tumors lack this ability Sca1+/cKit- BMCs were isolated from young and old mice bearing Matrigel control or size-matched primary tumors by FACS directly into RLT Plus Buffer (Qiagen Rneasy Plus Micro Kit)

2016-07-21 | E-GEOD-74120 | biostudies-arrayexpress

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