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Neoantigen-Specific CD8 T Cells with High Structural Avidity Preferentially Reside in and Eliminate Tumors

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

ORGANISM(S): Homo sapiens

PROVIDER: GSE232447 | GEO | 2023/05/18

REPOSITORIES: GEO

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Neoantigen-specific CD8 T cells with high structural avidity preferentially reside in and eliminate tumors.

Project description: Not available

| S-EPMC10244384 | biostudies-literature

Neoantigen-Specific CD8 T Cells with High Structural Avidity Preferentially Reside in and Eliminate Tumors (VDJ)

Project description:The success of cancer immunotherapy depends in part on the strength of antigen recognition by T cells. We characterized the T cell receptor (TCR) functional (antigen sensitivity) and structural (monomeric pMHC-TCR off-rates) avidities of 371 CD8 T cell clones specific for neoantigens, tumor-associated antigens (TAAs) or viral antigens isolated from tumors or blood of patients and healthy subjects. T cells from tumors exhibit stronger functional and structural avidity than their blood counterparts. Relative to TAA, neoantigen-specific T cells are of higher structural avidity and, consistently, are preferentially detected in tumors. Effective tumor infiltration in mice models is associated with high structural avidity and CXCR3 expression. Based on TCRs biophysicochemical properties, we derived and applied an in silico model predicting TCR structural avidity and validated the enrichment in high avidity T cells in patients’ tumors. These observations indicate a direct relationship between neoantigen recognition, T cell functionality and tumor infiltration. These results delineate a rational approach to identify potent T cells for personalized cancer immunotherapy.

2023-05-18 | GSE232446 | GEO

Neoantigen-Specific CD8 T Cells with High Structural Avidity Preferentially Reside in and Eliminate Tumors (GEX)

2023-05-18 | GSE232444 | GEO

Neoantigen-Specific CD8 T Cells with High Structural Avidity Preferentially Reside in and Eliminate Tumors

Project description:Neoantigen-Specific CD8 T Cells with High Structural Avidity Preferentially Reside in and Eliminate Tumors

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Neoantigen-Specific CD8 T Cells with High Structural Avidity Preferentially Reside in and Eliminate Tumors (VDJ)

Project description:Neoantigen-Specific CD8 T Cells with High Structural Avidity Preferentially Reside in and Eliminate Tumors (VDJ)

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Neoantigen-Specific CD8 T Cells with High Structural Avidity Preferentially Reside in and Eliminate Tumors (GEX)

Project description:Neoantigen-Specific CD8 T Cells with High Structural Avidity Preferentially Reside in and Eliminate Tumors (GEX)

| PRJNA971996 | ENA

Apoptosis-regulated low-avidity cancer-specific CD8(+) T cells can be rescued to eliminate HER2/neu-expressing tumors by costimulatory agonists in tolerized mice.

Project description: Not available

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High avidity CD8+ T cells efficiently eliminate motile HIV-infected targets and execute a locally focused program of anti-viral function.

Project description: Not available

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Apoptosis-regulated low avidity cancer-specific CD8+ T cells can be rescued to eliminate HER-2/neu expressing tumors by costimulatory agonists in tolerized mice

Project description:A major barrier of vaccines as cancer treatment is their failure to activate and maintain a complete cancer-specific CD8+ effector T cell repertoire. Low avidity T cells are more likely to escape clonal deletion in the thymus when compared to higher avidity T cells, and therefore comprise the major population of effector T cells available for activation in cancer patients. However, low avidity T cells fail to traffic into the tumor microenvironment and function in eradicating tumor under optimal vaccination conditions as opposed to higher avidity T cells that escape clonal deletion and do function in tumor killing. We utilized high and low avidity TCR transgenic CD8+ T cells specific for the immunodominant epitope of HER-2/neu (RNEU420-429) to identify signaling pathways responsible for the inferior activity of low avidity T cells. Adoptive transfer of these cells into tumor-bearing vaccinated mice identified members of apoptosis pathways as being upregulated in low avidity T cells. The increased expression of pro-apoptotic proteins by low avidity T cells promoted their own cell death and also that of other tumor-specific CD8+ T cells within their local environment. Importantly, this pro-apoptotic effect was overcome using a strong costimulatory signal that prevents activation-induced cell death and enables low avidity T cells to traffic into the tumor and assist in tumor clearance. These findings identify new therapeutic opportunities for activating the most potent anticancer T cell responses. High and low avidity T cells were isolated from TCR transgenic mice and adoptively transferred into Cy-treated, vaccinated, neu-N mice. Three days after adoptive transfer T cells were isolated from the tumor draining nodes and RNA was extracted for gene expression analysis.

2014-01-14 | E-GEOD-54020 | biostudies-arrayexpress

CD4+ T Cell Help Selectively Enhances High-Avidity Tumor Antigen-Specific CD8+ T Cells.

Project description: Not available

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