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Hallmarks of CD8 T cell dysfunction are established within hours of tumor antigen encounter

ABSTRACT: RNA-SEQ analysis of antigen-specific CD8 T cells sorted from murine liver tumors and from the spleens of Listeria-infected mice at different early timepoints following adoptive transfer. We sequenced naive antigen-specific CD8 T cells from spleens for comparison.

ORGANISM(S): Mus musculus

PROVIDER: GSE209711 | GEO | 2023/07/10

REPOSITORIES: GEO

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Hallmarks of CD8 T cell dysfunction are established within hours of tumor antigen encounter

Project description:ATAC-SEQ analysis of antigen-specific CD8 T cells sorted from murine liver tumors and from the spleens of Listeria-infected mice at different early timepoints following adoptive transfer. We sequenced naive antigen-specific CD8 T cells from spleens for comparison. We also sorted tumor-infiltrating antigen-specific CD8 T cells that were removed from tumors and parked in tumor-free hosts for 5 days. The overall goal of this study was to determine the earliest chromatin remodeling events in CD8 T cells activated and differentiating in late tumor-bearing hosts or in infected mice and to determine the extent to which tumor-induced chromatin remodeling was "imprinted."

2023-07-10 | GSE209710 | GEO

Whole-genome microarray analysis of primary, secondary, tertiary and quaternary memory CD8 T cells

Project description:The transcriptome of naive OT-I T cells was compared to memory CD8 T cells after 1, 2, 3, or 4 infection with ovalbumin expressing Listeria monocytogenes (LM-OVA). Naive Thy1.1 OT-I T cells were adoptively transferred into Thy1.2 naive hosts prior to infection with LM-OVA. The resulting memory CD8 T cell population was again adoptively transferred into naive hosts and the recipient mice were again infected with LM-OVA. The adoptive transfer was repeated up to four times to generate memory CD8 T cells with up to four consecutive antigen stimulations. Three individual mice were analyzed for each group. For quaternary memory CD8 T cells, spleens from two to three mice were pooled for each sample. Naive OT-I T cells served as control samples. http://dx.doi.org/10.1016/j.immuni.2010.06.014

2010-07-09 | E-GEOD-21360 | biostudies-arrayexpress

Hallmarks of CD8 T cell dysfunction are established within hours of tumor antigen encounter prior to cell division

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

2023-07-10 | GSE209712 | GEO

Tumor-specific CD4+ T cells eradicate established melanoma

Project description:Adoptive transfer of CD4+ T cells (TRP-1 CD4+ T cells) specific for tyrp-1 (tyrosinase-related protein 1) eradicate established tumors (melanoma) in lymphopenic RAG-/- hosts. In vitro differentiated CD8+ T cells have been the primary focus of immunotherapy of cancer with little focus on CD4+ T cells. Immunotherapy involving in vitro differentiated T cells given after lymphodepleting regimens significantly augments antitumor immunity in animals and human patients with cancer. However, the mechanisms by which lymphopenia augments adoptive cell therapy and the means of properly differentiating T cells in vitro are still emerging. We demonstrate that naïve tumor/self-specific CD4+ T cells naturally differentiated into T helper type 1 (Th1) cytotoxic T cells in vivo and caused the regression of established tumors and depigmentation in lymphopenic hosts. Therapy was independent of vaccination, exogenous cytokine support, CD8+-, B-, NK and NK-T cells. Proper activation of CD4+ T cells in vivo was important for tumor clearance as naïve tumor-specific CD4+ T cells could not completely treat tumor in lymphopenic common gamma chain-deficient (gc-/-) hosts. gc signaling in the tumor-bearing host was important for survival and proper differentiation of adoptively transferred tumor-specific CD4+ T cells. Thus, these data provide a platform for designing immunotherapies that incorporate tumor/self-reactive CD4+ T cells. 2 x 10^5 sorted TRP-1 CD4+ T cells were transferred i.v. into tumor-bearing RAG-/- hosts on day 7-10 after tumor challenge, and ~1 x 10^6 CD4+ T cells were isolated 1 week later by flow sorting from pooled lymph nodes (LN) or spleens. Dye-swaps were performed.

2010-01-14 | E-GEOD-19904 | biostudies-arrayexpress

Transcriptomics coupled proteomics reveals the critical signaling pathways regulating OVA antigen-specific CD8+ T cells in mouse spleen and liver

Project description:Antigen-specific T cells are particularly important for eliminating bacterial infection, and the dynamics in this process help uncover the mechanisms by which bacteria are eliminated.This study used MHC class I tetramers to recognize the antigen OVA antigen-specific CD8+ T cells in mouse spleen and liver. Then combined the RNAseq and LC-MS/MS analysis to track the changes of the OVA antigen-specific CD8+ T cells at different time points (5 days,7 days, and 14 days post listeria infection).Transcriptomics coupled proteomics reveals the key signaling pathways to regulate antigen-specific CD8+ T cells by infection of Listeria monocytogenes expressing the OVA protein in mouse spleen and liver.

2024-03-26 | PXD050970 | iProX

Nanostring analysis of human SUV39H1-knockout CAR T compared to control CAR T cells (mock) at different timepoint

Project description:Failure of adoptive T cell therapies in cancer patients is linked to limited T cell expansion and persistence, even in memory-prone 41BB-(BBz)-based chimeric antigen receptor (CAR) T cells. In murine CD8+ T cells, SUV39H1 promotes differentiation and expansion of effector CD8+ T cells during acute infection by Listeria monocytogenes by silencing stemness and memory genes (Pace et al. Science, 2018). The purpuse of this study is to investigate the transcriptomic differences of SUV39H1 knock-out versus mock human 41BBz-CAR T cells by Nanostring at different cycles of restimulation.

2023-10-31 | GSE244030 | GEO

Single cell RNAseq integrates T cell phenotypes associated with Listeria infection in mice

Project description:Mice were inoculated with Listeria by i.p. injection on days 0 and 11. On day 18, FSC(high)CD4(+)CD8(-)B220(-)MHCII(-) T cells were FACS-sorted from spleens for single cell RNAseq.

2018-07-17 | GSE117166 | GEO

Transcriptome Sequencing Reveals Molecular Signatures of Antigen-encountering T cells in Adoptive transfer Murine Heart Transplantation Model

Project description:The purpose of this study was to identify the molecular signatures of antigen-encountering T cells, we established the adoptive transfer murine heterotopic heart transplantation model and isolated TEa cells from spleens for RNA sequencing.

2024-01-06 | GSE216869 | GEO

Expression data from WT and Foxo1 KO CD8+ KLRG1high or KLRG1low populations after LCMV infection

Project description:The forkhead O transcription factors (FOXO) integrate a range of extracellular signals including growth factor signaling, inflammation, oxidative stress and nutrient availability, to substantially alter the program of gene expression and modulate cell survival, cell cycle progression, and many cell-type specific responses yet to be unraveled. Naive antigen-specific CD8+ T cells undergo a rapid expansion and arming of effector function within days of pathogen exposure, but in addition, by the peak of expansion, they form precursors to memory T cells capable of self-renewal and indefinite survival. We used microarrays to determine whether FOXO1 broadly affects effector and memory differentiation, and to what extent FOXO1 determines the program of memory T cell gene expression. To obtain an unbiased analysis of genes differentially expressed in antigen-specific Foxo1-/- CD8+ T cells responding to infection, we obtained RNA and performed Affymetrix microarray analysis from KLRG1low and KLRG1high FACS-sorted congenically-marked WT and Foxo1-/- P14 cells obtained from mixed transfers, eight days post-infection with LCMV-Armstrong. We carried out gene deletion in Rosa26Cre-ERT2 Foxo1f/f (Foxo1-/-) P14 mice just prior to adoptive transfer (Kerdiles et al., 2009), and transfer equal numbers of P14 cells from the spleens of KO (Foxo1-/- P14) and WT P14 mice. Day8 post infection

2013-04-13 | E-GEOD-46025 | biostudies-arrayexpress

Hexokinase 2 is dispensable for T cell-dependent immunity

Project description:Hexokinase 2 (HK2) is one the most highly upregulated enzymes in glycolysis in activated T cells and cancer cells. We genetically abolished HK2 expression in T cells in vivo and infected mice with LCMV to induce T cell proliferation. CD8+ T cells from were sorted from spleens of WT and HK2 null mice 8 days after infection. Additionally, WT CD8+ T cells were compared to WT primary T cell acute lymphoblastic leukemia (T-ALL). T-ALL cells were sorted from spleens of mice 6 weeks after adoptive transfer of bone marrow that overexpresses mutant Notch1 (Notch1-deltaE).

2018-08-13 | GSE118326 | GEO

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