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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE236825 | GEO | 2024/01/11

REPOSITORIES: GEO

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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]

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

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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.

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Acquisition of suppressive function by conventional T cells limits antitumor immunity upon T<sub>reg</sub> depletion.

Project description: Not available

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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]

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

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

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

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Induction of antigen-specific Treg cells in treating autoimmune uveitis via bystander suppressive pathways without compromising anti-tumor immunity.

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