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Acquisition of suppressive function by CD4+ conventional T cells limits anti-tumor immunity driven by Treg depletion [RNA-seq II]

ABSTRACT: Acquisition of suppressive function by CD4+ conventional T cells limits anti-tumor immunity driven by Treg depletion [RNA-seq II]

PROVIDER: PRJNA994054 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25247875.fastq.gz	Fastqsanger.gz
	SRR25247875_1.fastq.gz	Fastqsanger.gz
	SRR25247875_2.fastq.gz	Fastqsanger.gz
	SRR25247876.fastq.gz	Fastqsanger.gz
	SRR25247876_1.fastq.gz	Fastqsanger.gz

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Acquisition of suppressive function by CD4+ conventional T cells limits anti-tumor immunity driven by Treg depletion [scRNA-seq]

Project description:Regulatory T (Treg) cells are essential for immune homeostasis but inhibit immune rejection of cancer. Strategies to disrupt Treg-mediated cancer immunosuppression have been met with limited clinical success, but the underlying mechanisms for this failure are poorly understood. By modeling Treg-targeted immunotherapy in mice, we find that a subset of CD4+ Foxp3- conventional T (Tconv) cells with potent suppressive function undergoes activation and expansion upon depletion of Foxp3+ Treg cells and limits therapeutic efficacy. We noted that Foxp3- Tconv cells within tumors adopt a Treg-like transcriptional profile upon Treg depletion and acquire suppressive function. This is attributable to a Th2-like subset of CD4+ Tconv cells marked by expression of (C-C motif) receptor 8 (CCR8) and enriched in Treg-associated transcripts. CCR8+ Tconv cells are found in mouse and human tumors. Upon Treg depletion, CCR8+ Tconv cells undergo systemic and intratumoral activation and expansion, resulting in IL-10 dependent suppression of anti-tumor immunity. Consequently, conditional deletion of Il10 within T cells augments anti-tumor efficacy upon Treg-depletion in mice, and antibody blockade of IL-10 signaling synergizes with Treg depletion to overcome treatment resistance. These findings reveal a secondary layer of immunosuppression by Tconv cells released upon therapeutic Treg depletion and suggest that broader consideration of suppressive function within the T cell lineage is required for development of effective Treg-targeted therapies.

2024-01-11 | GSE236824 | GEO

Acquisition of suppressive function by CD4+ conventional T cells limits anti-tumor immunity driven by Treg depletion [RNA-seq]

2024-01-11 | GSE236823 | GEO

Acquisition of suppressive function by CD4+ conventional T cells limits anti-tumor immunity driven by Treg depletion.

Project description:Acquisition of suppressive function by CD4+ conventional T cells limits anti-tumor immunity driven by Treg depletion.

| PRJNA992480 | ENA

Acquisition of suppressive function by CD4+ conventional T cells limits anti-tumor immunity driven by Treg depletion [RNA-seq II]

2024-01-11 | GSE237140 | GEO

Acquisition of suppressive function by CD4+ conventional T cells limits anti-tumor immunity driven by Treg depletion [RNA-seq]

Project description:Acquisition of suppressive function by CD4+ conventional T cells limits anti-tumor immunity driven by Treg depletion [RNA-seq]

| PRJNA992496 | ENA

Acquisition of suppressive function by CD4+ conventional T cells limits anti-tumor immunity driven by Treg depletion [scRNA-seq]

Project description:Acquisition of suppressive function by CD4+ conventional T cells limits anti-tumor immunity driven by Treg depletion [scRNA-seq]

| PRJNA992495 | ENA

Transcriptional correlates of FOXP3 expression in suppressive and non-suppressive primary human Treg cell clones.

Project description:Analysis of the transcriptional correlates of FOXP3 expression in suppressive and non-suppressive primary human Treg cell clones. Individual CD4+CD25High or Cd4+CD25- T cells were isolated from human PBMCs and expanded in vitro. After 3 weeks of expansion, individual clones were analysed for FOXP3 expression and in vitro suppressive activity against freshly sorted allogeneic effector T cells. This study analyses the total RNA isolated from FOXP3+ clones with suppressive potency to their non-suppressive counterparts. The resutls of this study should provide insights into the molecular pathways linking FOXP3 expression to distinct aspects of Treg phenotype and function. Total RNA obtained from individual clones of primary human regulatory and effector CD4+T cells.

2015-05-06 | E-GEOD-65650 | biostudies-arrayexpress

Transcriptional correlates of FOXP3 expression in suppressive and non-suppressive primary human Treg cell clones.

2015-05-06 | GSE65650 | GEO

Acquisition of suppressive function by CD4+ conventional T cells limits anti-tumor immunity driven by Treg depletion.

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

2024-01-11 | GSE236825 | GEO

Gene expression by Treg subsets

Project description:Thymic-derived natural T regulatory cells (nTregs) are characterized by functional and phenotypic heterogeneity. Recently, a small fraction of peripheral Tregs have been shown to express Klrg1, but it remains unclear the extent Klrg1 defines a unique Treg subset. Here we show that Klrg1+ Tregs represent a terminally differentiated Treg subset derived from Klrg1- Tregs. This subset is a recent antigen-responsive and a highly activated short-lived Treg population that expresses enhanced levels of Treg suppressive molecules and that preferentially resides within mucosal tissues. The development of Klrg1+ Tregs also requires extensive IL-2R signaling. This activity represents a distinct function for IL-2, independent from its contribution to Treg homeostasis and competitive fitness. These and other properties are analogous to terminally differentiated short-lived CD8+ T effector cells. Our findings suggest that an important pathway driving antigen-activated conventional T lymphocytes also operates for Tregs. Gene expression analysis was performed of this and other Treg subsets based on expression of CD62L, CD69, and Klrg1 to define the molecular properties of Klrg1+ Tregs and its relationship to other Treg subsets found in the peripheral immune tissues. Mice were euthanized, spleen cell preparations were made, and each Treg subset was isolated by FACS cell sorting. RNA was immediately prepared for processing.

2012-08-06 | E-GEOD-36527 | biostudies-arrayexpress

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