Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Single cell transcriptomic and T cell repertoire analysis reveals trajectory of tumor - infiltrating lymphocyte states in pancreatic cancer

ABSTRACT: The CD8+ TIL contained a putative transitional GZMK+ population based on TCR clonotype sharing, and cell-state trajectory analysis showed similarity to a GZMB+PRF1+ cytotoxic and a CXCL13+ dysfunctional population. Statistical analysis suggested that certain TIL states, such as dysfunctional and inhibitory populations, often occurred together. Finally, analysis of cultured TIL revealed that high-frequency clones from effector populations were preferentially expanded. These data provide a framework for understanding the PDAC TIL landscape for future TIL use in immunotherapy for PDAC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE211644 | GEO | 2022/09/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Transcriptional Regulation of HL60 Neutrophil Differentiation: Promyelocyte trajectory vs. Neutrophil trajectory

Project description:Using the HL60 multipotent promyelocytic leukemia cell line, we performed experiments that lead to two different cell fate attractors by treatments of varying dosage and duration of the differentiation agent all-trans-retinoic acid (ATRA). The dosage and duration combinations corresponding to the two treatments were chosen by means of of cytometric measurements of CD11b, a well-known early differentiation marker, such that the two populations are poised at the same stage of differentiation. Using the selected treatment combinations, one population proceeds toward the terminally differentiated neutrophil attractor while the other population reverts back toward the undifferentiated promyelocytic attractor. We monitored the gene expression changes in the two populations after their respective treatments over a period of five days and identified a set of genes that diverged in their expression; a subset of which promotes neutrophil differentiation while the other represses cell cycle progression. By employing promoter based transcription factor binding site analysis, we found enrichment of transcription factors functionally linked to tumor progression, cell cycle, and development. Keywords: Time course, dose response Untreated HL60 cells are hybrized on the channel 1 with Cy3, ATRA-Treated HL60 cells are hybridized on channel 2 with Cy5. HK60 cells were treated with high dosage/short duration and low dosage/long duration to achieve 55% of CD11b+ cells. These positive cells were then isolated and culture in fresh media and total RNA were isolated for comparison. Cells treated with high dosage/short duration treatment proceed toward the neutrophil attractor while cells treated with the low dosage/long duration treatment revert back toward the promyelocyte attractor.

2008-11-19 | E-GEOD-13673 | biostudies-arrayexpress

Transcriptional Regulation of HL60 Neutrophil Differentiation: Promyelocyte trajectory vs. Neutrophil trajectory

2008-11-20 | GSE13673 | GEO

Immune profile and mitotic index of metastatic melanoma lesions enhance clinical staging in predicting patient survival.

Project description:Although remission rates for metastatic melanoma are generally very poor, some patients can survive for prolonged periods following metastasis. We used gene expression profiling, mitotic index (MI), and quantification of tumor infiltrating leukocytes (TILs) and CD3+ cells in metastatic lesions to search for a molecular basis for this observation and to develop improved methods for predicting patient survival. We identified a group of 266 genes associated with postrecurrence survival. Genes positively associated with survival were predominantly immune response related (e.g., ICOS, CD3d, ZAP70, TRAT1, TARP, GZMK, LCK, CD2, CXCL13, CCL19, CCR7, VCAM1) while genes negatively associated with survival were cell proliferation related (e.g., PDE4D, CDK2, GREF1, NUSAP1, SPC24). Identification of genes associated with survival of metastatic melanoma Survival Analysis was performed using Statistical Analysis of Microarrays B D denotes same patient with multiple reccurences

2009-11-30 | E-GEOD-19234 | biostudies-arrayexpress

Gene expression of dysfunctional CD8+ T cells from the tumor microenvironment

Project description:Although the presence of tumor-infiltrating lymphocytes (TILs) indicates an endogenous anti-tumor response, immune regulatory pathways can subvert the effector phase and enable tumor escape. Negative regulatory pathways include extrinsic suppression mechanisms but also a T cell-intrinsic dysfunctional state. A more detailed study has been hampered by a lack of cell surface markers defining dysfunctional TILs, and it is clear that PD-1 alone is not sufficient. Recently, we identified the transcription factor Egr2 as a critical component in controlling the anergic state in vitro. In the current study we show that the Egr2-driven cell surface proteins, LAG-3 and 4-1BB, identify dysfunctional tumor antigen-specific CD8+ TIL. Co-expression of 4-1BB and LAG-3 was seen on a majority of CD8+ TIL but not in lymphoid organs. Functional analysis revealed defective IL-2 and TNF-α production yet retained expression of IFN-γ and Treg-recruiting chemokines. Transcriptional and phenotypic characterization revealed co-expression of multiple additional co-stimulatory and co-inhibitory receptors. Administration of anti-LAG-3 plus anti-4-1BB mAbs was therapeutic against tumors in vivo, which correlated with a reversal of TIL dysfunction and restored effector phenotype. Our results indicate that co-expression of LAG-3 and 4-1BB characterize dysfunctional T cells within tumors, and that targeting these receptors has therapeutic utility.

2016-04-05 | GSE79919 | GEO

Re-evaluating the melanoma TIL compartment and its unexpected spectrum of exhausted and functional T cells

Project description:Significant heterogeneity exists within the tumor infiltrating CD8 T cell population, and exhausted T cells harbor a subpopulation that may be replicating and retain signatures of activation, with potential functional consequences in tumor progression. Dysfunctional immunity in the tumor microenvironment is associated with poor cancer outcomes, making exploration of these exhausted but activated (Tex/act) subpopulations critical to the improvement of therapeutic approaches. To investigate mechanisms associated with Tex/act cells, we sorted and performed transcriptional profiling of CD8+ tumor infiltrating lymphocytes (TIL) coexpressing the exhaustion markers PD-1 and TIM-3, from large volume melanoma tumors. We additionally performed immunologic phenotyping and functional validation, including at the single cell level, to identify potential mechanisms that underlie their dysfunctional phenotype. We identified novel dysregulated pathways in CD8+PD-1+TIM-3+ cells that have not been well studied in TIL; these include bile acid and peroxisome pathway-related metabolism, and mammalian target of rapamycin (mTOR) signaling pathways, which are highly correlated with immune checkpoint receptor expression. Through bioinformatic integration of immunophenotypic data and network analysis, we propose unexpected targets for therapies to rescue the immune response to tumors in melanoma.

2023-12-06 | GSE230864 | GEO

IL-33 provision by reprogrammed tumor fibroblastic stromal cells promotes local T cell activity and facilitates melanoma eradication

Project description:The tumor microenvironment (TME) is a complex mixture of tumor cells, immune cells, endothelial cells and fibroblastic stroma cells (FSC). While cancer-associated fibroblasts are generally seen as a tumor-promoting entity, it is conceivable that distinct FSC populations within the TME contribute to immune-mediated tumor control. Here, we show that intra-tumoral injection of a recombinant LCMV-based vaccine vector (r3LCMV) expressing the melanocyte differentiation antigen TRP2 results in T cell-dependent eradication of melanomas. Analysis of the TME revealed that viral vector transduction precipitates activation of particular FSC subsets. Using single-cell RNA-seq analysis, we identified a Cxcl13-expressing FSC population with a pronounced immune-stimulatory signature and increased expression of the inflammatory cytokine IL-33. Genetic ablation of Il33 in Cxcl13-Cre+ FSC impeded functionality of intratumoral T cells and consequently tumor control. Thus, reprogramming of distinct FSC subsets in the TME through LCMV-based vectors efficiently promotes tumor eradication by locally sustaining the activity of tumor-specific T cells.

2021-07-03 | E-MTAB-9407 | biostudies-arrayexpress

CD8+ Tumor-Infiltrating Lymphocyte Abundance is a Positive Prognostic Indicator in Nasopharyngeal Cancer

Project description:A retrospective tissue study to explore the prognostic significance of tumor-infiltrating lymphocyte (TIL) populations in Nasopharyngeal Cancer, using a combination of RNA sequencing and immunohistochemistry.

2022-09-01 | E-MTAB-11963 | biostudies-arrayexpress

Deep Sequencing of Korean Jindo Dog Reveals Evolutionary Trajectory of Coat Color Variations

Project description:The inherent diversity of canines is closely intertwined with the unique color patterns of each dog population. These variations in color patterns are believed to have originated through mutations and selective breeding practices that occurred during and after the domestication of dogs from wolves. To address the significant gaps that persist in comprehending the evolutionary processes that underlie the development of these patterns, we generated and analyzed deep-sequenced genomes of 113 Korean indigenous Jindo dogs that represent five distinct color patterns to identify the associated mutations in CBD103, ASIP, and MC1R. The degree of linkage disequilibrium and estimated allelic ages consistently indicate that the black-and-tan dogs descend from the first major founding population on Jindo island, compatible with the documented literature. We additionally demonstrate that black-and-tan dogs, in contrast to other color variations within the breed, exhibit a closer genetic affinity to ancient wolves from western Eurasia than those from eastern Eurasia. Lastly, population-specific genetic variants with moderate effects were identified, particularly in loci associated with traits underlying body size and behavioral variations, potentially explaining the observed phenotypic diversity based on coat colors. Overall, comparisons of whole genome sequences of each coat color population diverged from the same breed provided an unprecedented glimpse into the properties of evolutionary processes maintaining variation in Korean Jindo dog populations that were previously inaccessible.

2024-04-05 | E-MTAB-13939 | biostudies-arrayexpress

CD8+/CD103+ tumor-infiltrating lymphocytes are tumor-specific tissue-resident memory T cells and a prognostic factor for survival in lung cancer patients

Project description:We had previously demonstrated the role of CD103 integrin on lung tumor-infiltrating lymphocyte (TIL) clones in promoting specific TCR-mediated epithelial tumor cell cytotoxicity. However, the contribution of CD103 on intratumoral T-cell distribution and functions, and the prognosis significance of TIL subpopulations in non-small cell lung carcinoma (NSCLC) have thus far not been systematically addressed. Here we investigate the transcriptomic profil of these cell population, using PBMC cells as control.

2015-06-29 | E-MTAB-3266 | biostudies-arrayexpress

Tumor-induced double positive T cells display distinct lineage commitment mechanisms and functions (2)

Project description:Here we report transcriptional and TCR specificities associated with melanoma patient TIL populations.

2022-05-20 | GSE203183 | GEO