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Detecting Tumor Specific Antigen-Reactive T cells from Tumor Infiltrating Lymphocytes via Interaction Dependent Fucosyl-biotinylation [TCR-seq]

ABSTRACT: Detecting Tumor Specific Antigen-Reactive T cells from Tumor Infiltrating Lymphocytes via Interaction Dependent Fucosyl-biotinylation [TCR-seq]

PROVIDER: PRJNA646760 | ENA |

REPOSITORIES: ENA

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Detecting Tumor Specific Antigen-Reactive T cells from Tumor Infiltrating Lymphocytes via Interaction Dependent Fucosyl-biotinylation [TCR-seq]

Project description:Reactivation and clonal expansion of tumor specific antigen (TSA)-reactive T cells are key to the success of checkpoint blockade and adoptive transfer of tumor-infiltrating lymphocyte (TIL) based therapies. There are no reliable markers to specifically identify the repertoire of TSA-reactive T cells due to their heterogeneous composition. Here we introduce FucoID as a general platform to detect endogenous antigen-specific T cells and study their biology. Through this interaction dependent labeling approach, TSA-reactive T cells can be detected and separated from bystander T cells in primary tumor digests based on their cell-surface enzymatic fucosyl-biotinylation. Compared to bystander TILs, TSA-reactive TILs possess a unique gene features according to RNA-seq.

2020-10-22 | GSE154604 | GEO

Detecting Tumor Specific Antigen-Reactive T cells from Tumor Infiltrating Lymphocytes via Interaction Dependent Fucosyl-biotinylation [RNA-seq]

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Detecting Tumor Specific Antigen-Reactive T cells from Tumor Infiltrating Lymphocytes via Interaction Dependent Fucosyl-biotinylation [RNA-seq]

Project description:Detecting Tumor Specific Antigen-Reactive T cells from Tumor Infiltrating Lymphocytes via Interaction Dependent Fucosyl-biotinylation [RNA-seq]

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Detecting Tumor Antigen-Specific T Cells via Interaction-Dependent Fucosyl-Biotinylation

Project description:Detecting Tumor Antigen-Specific T Cells via Interaction-Dependent Fucosyl-Biotinylation

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RNA Profiling in Patients' tumor infiltrating lymphocytes

Project description:Identifying tumor antigen-specific T cells from cancer patients has been a goal of tumor immunologists for several decades. Co-expression of CD103 and CD39 on CD8 TIL highly enriches for tumor-reactive T cells. CD39+CD103+ CD8 TIL have a distinct TCR repertoire compared to other CD8 TIL subsets and are clonally expanded within the tumor. They are highly enriched for tumor antigen recognition and efficiently killed autologous tumor cells. Patients with head and neck cancer whose CD8 TIL contained a higher frequency of CD39+CD103+ cells experienced a greater overall survival. This work describes a simple and effective method for detecting tumor-reactive CD8 TIL.

2018-05-26 | GSE114944 | GEO

Tumor-reactive clonotype dynamics dictate clinical response to TIL therapy in melanoma [TCR-Seq]

Project description:Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) is effective in cancer patients, yet the profiles, specificity and dynamics of tumor clonotypes remain opaque. Using single-cell RNA/TCR-sequencing, clonotypes were tracked from baseline tumors to ACT products (ACTP) and post-ACT blood and tumor samples from 13 metastatic melanoma patients (NCT03475134). Furthermore, a predictor of tumor-reactive clonotypes was derived from the transcriptomic profiles of tumor-specific or bystander clones. Patients with clinical responses had tumors enriched in tumor-reactive TILs, preferentially expanding in-vitro to generate larger and more tumoricidal products and preferentially re-infiltrating tumors post-ACT. Conversely, lack of responses was associated with tumors devoid of tumor-reactive clonotypes and with cell products mostly composed of blood-borne clonotypes. The exhaustion state characterizing intratumoral tumor-reactive TILs was attenuated during in-vitro expansion and restored after tumor re-engraftment only in responders. Thus, tumor-reactive clonotypes drive clinical response to TIL therapy, providing insight to select patients or improve TILs’ culture.

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Clonal spreading of tumor-infiltrating T cells underlies the durable antitumor effects of PD-1 blockade and anti-CD4 monoclonal antibody: Bulk TCR sequencing

Project description:The repertoire of tumor-infiltrating T cells is a novel perspective to characterize effective anti-tumor T cell responses. Previous studies reported that the oligoclonal expansion in tumor T-cell repertoire is associated with anti-tumor effects. However, the contribution of the expansion of diverse T-cell clones remained unclear. We demonstrated that the polyclonal fraction of tumor-reactive T-cell repertoire consisting of relatively minor clones, increased in tumor-bearing mice treated with anti-PD-L1 or anti-CD4 monoclonal antibodies (mAbs), while the oligoclonal fraction consisting of major clones was unchanged. Moreover, the polyclonal fraction was enriched with progenitor exhausted T cells, essential for a durable anti-tumor response, and more dependent on CCR7+ migratory dendritic cells, responsible for priming tumor-reactive T cells in the tumor-draining lymph node (dLN). These results proposed that the expansion of diverse tumor-reactive clones, “clonal spreading,” is an important mechanism by which anti-PD-L1 and anti-CD4 treatments exert robust and durable anti-tumor T-cell responses.

2023-05-11 | GSE216795 | GEO

Detecting Tumor Antigen-Specific T Cells via Interaction-Dependent Fucosyl-Biotinylation

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

2020-10-22 | GSE154605 | GEO

Detecting Tumor Antigen-Specific T Cells via Interaction-Dependent Fucosyl-Biotinylation.

Project description: Not available

| S-EPMC7669731 | biostudies-literature

Gene-expression profiles of non-tumor-reactive CD8+ T cells

Project description:Non-tumor-reactive T cells are characterized by the inabilitzy to lyse autologous tumor cells, low to intermediate avidity TCRs and lack of NY-ESO-1 peptide tetramer binding. However most strikingly, non-tumor-reactive T cells are characterized by a molecular program associated with ‘division arrest anergy’ with elevated expression of the inhibitory molecule p27kip1. This is accompanied by elevated expression of inhibitory molecules and reduced levels of transcription factors involved in T cell activation. Frequency analysis of the inhibited T cell population using the established molecular fingerprint as a novel biomarker might be applied for cancer vaccine development and optimization. Keywords: cell type comparison

2009-06-15 | GSE11188 | GEO

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