Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA644867 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Tumor antigen specific CD8 Tissue Resident Memory (Trm) Cells
| PRJNA644934 | ENA
Project description:Single cell RNA-seq of tumor antigen specific CD8 Tissue Resident Memory (Trm) Cells
| PRJNA645094 | ENA
Project description:Tissue-resident memory (TRM) T cells are emerging as critical components of the immune response to cancer; yet, requirements for their ongoing function and maintenance remain unclear. Antigen presenting cells (APC) promote TRM cell differentiation and re-activation but have not been implicated in sustaining TRM cell responses. Here, we identified a novel role for dendritic cells in supporting tissue resident memory to melanoma. We showed that CD8 TRM cells remain in close proximity to dendritic cells in the skin. Depletion of CD11c+ cells results in rapid disaggregation and eventual loss of melanoma-specific TRM cells. Additionally, we determined that TRM migration and/or persistence requires chemotaxis and adhesion mediated by the CXCR6/CXCL16 axis. The interaction between CXCR6-expressing TRM cells and CXCL16-expressing APCs was found to be critical for sustaining TRM cell-mediated tumor protection. These findings substantially expand our knowledge of APC functions in tissue resident memory T cell homeostasis and longevity.
2021-07-29 | GSE180647 | GEO
Project description:Analyses of healthy tissue reveal signatures that identify resident memory CD8+ T cells (TRM), which survey tissues without recirculating. The density of TRM-phenotype cells within solid tumors correlates favorably with prognosis, suggesting that intratumoral residents control cancer. However, residence has not been directly tested and intratumoral TRM-phenotype cells could instead reflect aspects of the microenvironment that correlate with prognosis. Using a breast cancer model, we found that conventional TRM markers do not inform the tumor residence of either bystander or tumor-specific cells, which exhibit further distinct phenotypes in the tumor microenvironment and healthy mammary tissue. Rather, tumor-specific, stem-progenitor CD8+ T cells migrate to tumors and become resident while acquiring select markers of exhaustion. These data indicate that tonic antigen stimulation and the tumor environment drive distinct programs of residence compared to healthy tissues and that tumor immunity is sustained by continued migration of tumor-specific stem cells.
2023-06-02 | GSE231541 | GEO
Project description:Tissue-resident memory CD8+ T cells (Trm) provide host protection through continuous surveillance of non-lymphoid tissues. While the relevance of Trm in diverse diseases ranging from infection to cancer is appreciated, the development and functional heterogeneity of Trm remain poorly understood. Using single-cell RNA-sequencing (scRNA-seq) and genetic reporter mice, we identified discrete lineages of intestinal antigen-specific CD8+ T cells, including a Blimp1hiId3lo tissue-resident effector cell population most prominent in the early phase of acute viral and bacterial infections, and a molecularly distinct Blimp1loId3hi tissue-resident memory population that subsequently accumulated at later infection timepoints. These distinct Trm populations where characterized by unique transcriptional programs including differential roles for transcriptional regulators Blimp1, T-bet, Id2, and Id3 in supporting and maintaining intestinal Trm heterogeneity during infection. Extending our analysis to malignant tissue, we also identified discrete populations of effector-like and memory-like CD8+ T cell populations with tissue-resident gene-expression signatures within tumors that shared features of terminally-exhausted and progenitor-exhausted T cells, respectively. Clarification of CD8+ T cell ontogeny and heterogeneity in non-lymphoid tissues holds broad implications for enhancing vaccination and immunotherapy approaches.
2020-04-15 | GSE147263 | GEO
Project description:Tissue-resident memory CD8+ T cells (Trm) provide host protection through continuous surveillance of non-lymphoid tissues. While the relevance of Trm in diverse diseases ranging from infection to cancer is appreciated, the development and functional heterogeneity of Trm remain poorly understood. Using single-cell RNA-sequencing (scRNA-seq) and genetic reporter mice, we identified discrete lineages of intestinal antigen-specific CD8+ T cells, including a Blimp1hiId3lo tissue-resident effector cell population most prominent in the early phase of acute viral and bacterial infections, and a molecularly distinct Blimp1loId3hi tissue-resident memory population that subsequently accumulated at later infection timepoints. These distinct Trm populations where characterized by unique transcriptional programs including differential roles for transcriptional regulators Blimp1, T-bet, Id2, and Id3 in supporting and maintaining intestinal Trm heterogeneity during infection. Extending our analysis to malignant tissue, we also identified discrete populations of effector-like and memory-like CD8+ T cell populations with tissue-resident gene-expression signatures within tumors that shared features of terminally-exhausted and progenitor-exhausted T cells, respectively. Clarification of CD8+ T cell ontogeny and heterogeneity in non-lymphoid tissues holds broad implications for enhancing vaccination and immunotherapy approaches.
2020-04-15 | GSE147081 | GEO
Project description:Tissue-resident memory CD8+ T cells (Trm) provide host protection through continuous surveillance of non-lymphoid tissues. While the relevance of Trm in diverse diseases ranging from infection to cancer is appreciated, the development and functional heterogeneity of Trm remain poorly understood. Using single-cell RNA-sequencing (scRNA-seq) and genetic reporter mice, we identified discrete lineages of intestinal antigen-specific CD8+ T cells, including a Blimp1hiId3lo tissue-resident effector cell population most prominent in the early phase of acute viral and bacterial infections, and a molecularly distinct Blimp1loId3hi tissue-resident memory population that subsequently accumulated at later infection timepoints. These distinct Trm populations where characterized by unique transcriptional programs including differential roles for transcriptional regulators Blimp1, T-bet, Id2, and Id3 in supporting and maintaining intestinal Trm heterogeneity during infection. Extending our analysis to malignant tissue, we also identified discrete populations of effector-like and memory-like CD8+ T cell populations with tissue-resident gene-expression signatures within tumors that shared features of terminally-exhausted and progenitor-exhausted T cells, respectively. Clarification of CD8+ T cell ontogeny and heterogeneity in non-lymphoid tissues holds broad implications for enhancing vaccination and immunotherapy approaches.
2020-04-15 | GSE147080 | GEO
Project description:Tissue-resident memory CD8+ T cells (Trm) provide host protection through continuous surveillance of non-lymphoid tissues. While the relevance of Trm in diverse diseases ranging from infection to cancer is appreciated, the development and functional heterogeneity of Trm remain poorly understood. Using single-cell RNA-sequencing (scRNA-seq) and genetic reporter mice, we identified discrete lineages of intestinal antigen-specific CD8+ T cells, including a Blimp1hiId3lo tissue-resident effector cell population most prominent in the early phase of acute viral and bacterial infections, and a molecularly distinct Blimp1loId3hi tissue-resident memory population that subsequently accumulated at later infection timepoints. These distinct Trm populations where characterized by unique transcriptional programs including differential roles for transcriptional regulators Blimp1, T-bet, Id2, and Id3 in supporting and maintaining intestinal Trm heterogeneity during infection. Extending our analysis to malignant tissue, we also identified discrete populations of effector-like and memory-like CD8+ T cell populations with tissue-resident gene-expression signatures within tumors that shared features of terminally-exhausted and progenitor-exhausted T cells, respectively. Clarification of CD8+ T cell ontogeny and heterogeneity in non-lymphoid tissues holds broad implications for enhancing vaccination and immunotherapy approaches.
2020-04-15 | GSE147021 | GEO
Project description:Hepatocellular carcinoma (HCC) often develops following chronic hepatitis B virus (HBV) infection and responds poorly to immune checkpoint blockade. Here we examined the antigen specificities of HCC-infiltrating T cells and their relevance to tumor control. Using highly multiplexed peptide-MHC tetramer staining of unexpanded cells from blood, liver and tumor tissues from 46 HCC patients, we detected 91 different antigen-specific CD8+ T cell populations targeting HBV, neoantigen, tumor-associated and disease-unrelated antigens. Parallel high-dimensional analysis delineated five distinct antigen-specific tissue-resident memory T (Trm) cell populations. Intratumoral and intrahepatic HBV-specific T cells were enriched for two Trm cell subsets that were PD-1-low and TOX-low, despite being clonally expanded. High frequencies of intratumoral terminally exhausted T cells was uncommon. Patients with tumor-infiltrating HBV-specific CD8+ Trm cells exhibited longer-term relapse-free survival. Thus, non-terminally exhausted HBV-specific CD8+ Trm cells show hallmarks of active involvement and effective antitumor response, implying that these cells could be harnessed for therapeutic purposes.
2021-04-21 | GSE172400 | GEO
Project description:Current cancer immunotherapies promote recovery of CD103+ tissue-resident memory T cells (Trm) population of the tumor-infiltrating T lymphocytes (TILs). However, not all treated patients exhibit improved anti-tumor immunity and survival, likely due to the immunophenotypical diversity among the CD103+ Trm TILs. Utilising multifaceted proteomics approaches and patients’ clinical analyses, we discovered an unusual subset of CD8+ Trm TILs expressing non-canonical integrin β3 early during T cells activation. The integrin β3 surprisingly heterodimerises with CD103 on T cells, leading to unconventional granulysin-mediated cytotoxicity, elevated alternative bioenergy usage and efficient T cell migration, with minimal overall exhaustion. Importantly, early-stage non-small cell lung carcinoma (NSCLC) patients with enriched presence of integrin β3+CD103+ Trm TILs exhibited better clinical prognosis, with improved T cell immunophenotype, hence confirming the beneficial role of this unusual subset of Trm TILs. These unconventional anti-tumor T cell features provide new avenues and future opportunities for designing better translational immunotherapy strategies.
2024-02-14 | PXD031794 | Pride