Antigen-specific CD8+ T cells from tumor draining of melanoma bearing mice
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ABSTRACT:
PROVIDER: PRJNA746545 | ENA |
REPOSITORIES: ENA
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Project description:CD8+ T cell-mediated immune response plays a pivotal role in controlling tumor growth.However, within the tumor microenvironment (TME), prolonged antigen exposure, as well as immunosuppressive factors, drive infiltrated tumor-specific CD8+ T cells into a hyporesponsive state known as “exhaustion”. Notably, our current understanding of tumor-specific CD8+ T cells mainly comes from experiments focusing on tumor infiltrated T cells, less is known about those in tumor draining LNs. Hence, we profiled the chromosome accessibilities of antigen-specific CD8+ T cells from tumor draining LNs of melanoma bearing mice in this project, aiming to draw a comprehensive immune-atlas of tumor-specific CD8+ T cells during tumorigenesis.
2022-10-10 | GSE180084 | GEO
Project description:CD8+ T cell-mediated immune response plays a pivotal role in controlling tumor growth.However, within the tumor microenvironment (TME), prolonged antigen exposure, as well as immunosuppressive factors, drive infiltrated tumor-specific CD8+ T cells into a hyporesponsive state known as “exhaustion”. Notably, our current understanding of tumor-specific CD8+ T cells mainly comes from experiments focusing on tumor infiltrated T cells, less is known about those in tumor draining LNs. Hence, we profiled the chromosome accessibilities of antigen-specific CD8+ T cells from tumor draining LNs of melanoma bearing mice in this project, aiming to draw a comprehensive immune-atlas of tumor-specific CD8+ T cells during tumorigenesis.
2022-10-10 | GSE214384 | GEO
Project description:CD8+ T cell-mediated immune response plays a pivotal role in controlling tumor growth.However, within the tumor microenvironment (TME), prolonged antigen exposure, as well as immunosuppressive factors, drive infiltrated tumor-specific CD8+ T cells into a hyporesponsive state known as “exhaustion”. These Tex cells are mainly characterized by the sustained and elevated expression of a series of inhibitory receptors as well as the hierarchical loss of effector functions. Further, the impaired proliferative capacity of exhausted CD8+ T cells results in decreasing numbers of tumor-specific T cells, such that the residual CD8+ T cells within the TME can barely provide sufficient protective immunity against tumor progression. Thus, the maintenance or reinforcement of intratumoral antigen-specific CD8+ T cells is indispensable for tumor repression. Here, we profiled the transcriptional signatures of antigen-specific CD8+ T cells from tumor draining LN, TIL and PBMC of melanoma bearing mice at single-cell level, aiming to draw a comprehensive immune-atlas of tumor-specific CD8 T cells during tumorigenesis.
2022-10-10 | GSE180094 | GEO
Project description:ATAC-seq of antigen-specific CD8+ T cells from tumor draining LNs of melanoma bearing mice
| PRJNA746488 | ENA
Project description:ATAC-seq of antigen-specific CD8+ T cells from tumor draining LNs of melanoma bearing mice II
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Project description:scRNA-seq of antigen-specific CD8+ T cells from tumor draining LN, TIL and PBMC of melanoma bearing mice
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Project description:CD4+ T cells play a crucial role in tumor eradication. Employing single-cell RNA sequencing (scRNA-seq), we analyzed the cell states of CD45+ immune cells from tumors and draining lymph nodes in Trp1 CD4+ T cell-treated B16F10 melanoma-bearing mice. This investigation aims to enhance our understanding of how CD4 T cells mediate tumor regression.
2023-12-18 | GSE250511 | GEO
Project description:One key reason for T cell exhaustion is continuous antigen exposure. Early exhausted T cells can reverse exhaustion and differentiate into fully functional memory T cells if removed from persisting antigen stimulation. Therefore, this study viewed T cell exhaustion as an over-activation status induced by chronic antigen stimuli. This study hypothesized that blocking TCR signal intermittently to terminate over-activation signal can defer the developmental process of T cell exhaustion. In this study, B16F10 melanoma-bearing mice were treated with tacrolimus (FK506) every five days. The tumor size and tumor-infiltrating lymphocytes (TILs) were analyzed. We found that intermittent administration of tacrolimus significantly inhibited tumor growth, and this effect was mediated by CD8+T cells. Intermittent tacrolimus treatment facilitated the infiltration of CD8+TILs. RNA-seq and quantitative RT-PCR of sorted CD8+TILs showed the expression of Nr4a1 (an exhaustion-related transcription factor) and Ctla4 (a T cell inhibitory receptor) was remarkably downregulated. These results indicated that intermittently blocking TCR signal by tacrolimus can promote anti-tumor immunity and inhibit the tumor growth in melanoma-bearing mice, inhibiting the transcription of several exhaustion-related genes, such as Nr4a1 and Ctla4.
2022-02-03 | GSE190872 | GEO
Project description:The immune system undergoes a progressive functional remodeling with age, polarizing the immune responses toward a “killer” or “healer” phenotype. Understanding how the age bias shapes anti-tumor immunity is essential in designing effective immunotherapies. In this manuscript we explore the anti-tumor CD8+ T cell responses generated in young (prepubescent) and adult (pre-senescent) mice. Using an MHCI-deficient, trackable tumor model, we observed that tumor reactive CD8+ T cells that expanded in young tumor-bearing (TB) mice acquired a terminally differentiated phenotype characterized by overexpression of inhibitory receptors and the transcription factor Tox1. Furthermore, tumor infiltrating CD8+ T cells from young tumors yielded a poor cytokine response compared to CD8+ T cells infiltrating adult tumors. Young migratory dendritic cells (migDC) and mononuclear phagocytic cells (MPCs) infiltrating young tumors were more competent in capturing and cross-presenting tumor antigen, leading to enhanced priming of CD8+ T cells in the draining lymph nodes (dLNs), and their subsequent terminal differentiation in the tumors. Notably, single-cell transcriptional profiling of tumor infiltrating MPCs revealed that young MPCs are polarized toward an inflammatory, effector phenotype. Consistent with our observations in young vs adult TB mice, analysis of immune infiltrates from pediatric solid tumors revealed a significant correlation between tumor-infiltrating CD8+ T cells with an exhaustion phenotype and the frequency of PD-L1-expressing phagocytic cells. Collectively, these data indicate that the young microenvironment of an actively developing tissue contributes to the generation of an immune response skewed toward a terminal effector state, thus narrowing the window for immunotherapeutic interventions.
2022-02-28 | GSE188388 | GEO
Project description:The immune system undergoes a progressive functional remodeling with age, polarizing the immune responses toward a “killer” or “healer” phenotype. Understanding how the age bias shapes anti-tumor immunity is essential in designing effective immunotherapies. In this manuscript we explore the anti-tumor CD8+ T cell responses generated in young (prepubescent) and adult (pre-senescent) mice. Using an MHCI-deficient, trackable tumor model, we observed that tumor reactive CD8+ T cells that expanded in young tumor-bearing (TB) mice acquired a terminally differentiated phenotype characterized by overexpression of inhibitory receptors and the transcription factor Tox1. Furthermore, tumor infiltrating CD8+ T cells from young tumors yielded a poor cytokine response compared to CD8+ T cells infiltrating adult tumors. Young migratory dendritic cells (migDC) and mononuclear phagocytic cells (MPCs) infiltrating young tumors were more competent in capturing and cross-presenting tumor antigen, leading to enhanced priming of CD8+ T cells in the draining lymph nodes (dLNs), and their subsequent terminal differentiation in the tumors. Notably, single-cell transcriptional profiling of tumor infiltrating MPCs revealed that young MPCs are polarized toward an inflammatory, effector phenotype. Consistent with our observations in young vs adult TB mice, analysis of immune infiltrates from pediatric solid tumors revealed a significant correlation between tumor-infiltrating CD8+ T cells with an exhaustion phenotype and the frequency of PD-L1-expressing phagocytic cells. Collectively, these data indicate that the young microenvironment of an actively developing tissue contributes to the generation of an immune response skewed toward a terminal effector state, thus narrowing the window for immunotherapeutic interventions.
2022-02-28 | GSE188387 | GEO