CD8 TIL subsets isolation from early-stage, untreated NSCLC
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA974395 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24658682_1.fastq.gz | Fastqsanger.gz | |||
| SRR24658682_2.fastq.gz | Fastqsanger.gz | |||
| SRR24658683_1.fastq.gz | Fastqsanger.gz | |||
| SRR24658683_2.fastq.gz | Fastqsanger.gz | |||
| SRR24658684_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 20 |
Similar Datasets
Project description:The overall objective of this study was to characterize the diversity and ontogeny of CD8 T cells in untreated lung tumors. This was accomplished by performing bulk RNAseq and flow cytometry analysis on CD8+ T cell subsets isolated from tumor tissue, normal adjacent to tumor (juxta0 tissue samples from patients undergoing surgical resection for early-stage, untreated non-small-cell lung cancer (NSCLC).
2023-10-09 | GSE232899 | GEO
Project description:About 10% of all NSCLC patients respond to gefitnib treatment and all of these patients will acquire resistance to the EGFR TKI. We used microarray to look at global gene expression changes in untreated cells vs gefitinib treated cells to identify key characters for the acquisition of resistance. NSCLC cells, H322c, were cultured 4 days in media containing 1?M gefitinib or 0.1% DMSO as a control. On day 4, RNA was extracted and submitted for microarray hybridization.
2011-01-27 | E-GEOD-23206 | biostudies-arrayexpress
Project description:About 10% of all NSCLC patients respond to gefitnib treatment and all of these patients will acquire resistance to the EGFR TKI. We used microarray to look at global gene expression changes in untreated cells vs gefitinib treated cells to identify key characters for the acquisition of resistance.
2011-01-27 | GSE23206 | GEO
Project description:Teosinte Til 11 transcriptome sequencing
| PRJNA498523 | ENA
Project description:Tumor-infiltrating lymphocytes (TILs) are considered to be exhausted, lacking proliferative and effector functions, which impairs cancer immunity. We employed single-cell mass cytometry and tissue imaging technologies to dissect TILs in 25 resectable and 35 advanced non-small cell lung cancer (NSCLC) patients. We identified a phenotypically burn-out CD8 TIL subset (Ebo), specifically accumulated within the tumor microenvironment (TME). In contrast to exhausted T-cells, Ebo appears to be the most proliferative TIL subset. Furthermore, Ebo showed the highest expression of activation markers, but it was more apoptotic and produced less IFNg than other CD8 TIL subsets. Using a humanized patient-derived tumor xenograft model, we demonstrated that Ebo expansion occurred within the TME in a PD-pathway dependent manner. Importantly, Ebo abundance in baseline tumor tissues was associated with resistance to anti-PD therapy in NSCLC patients. Our study identified a dysfunctional TIL subset, distinct from exhausted T-cells, and implies strategies to overcome resistance in cancer immunotherapy.
2021-02-23 | GSE167235 | GEO
Project description:PURPOSE: Non-small cell lung cancers (NSCLC) comprise multiple distinct biological groups with different prognoses. For example, patients with epithelial-like (EL) tumors have a better prognosis and exhibit greater sensitivity to inhibitors of the epidermal growth factor receptor (EGFR) pathway than patients with mesenchymal-like (ML) tumors. Here we test the hypothesis that EL NSCLCs can be distinguished from ML NSCLCs on the basis of global DNA methylation patterns. EXPERIMENTAL DESIGN: To determine whether phenotypic subsets of NSCLC can be defined based on their DNA methylation patterns, we combined microfluidics-based gene expression analysis and genome-wide methylation profiling. We derived robust classifiers for both gene expression and methylation in cell lines and tested these classifiers in surgically resected NSCLC tumors. We validate our approach using quantitative RT-PCR and methylation specific PCR in formalin-fixed biopsies from NSCLC patients who went on to fail front-line chemotherapy. RESULTS: We show that patterns of methylation divide NSCLCs into EL and ML subsets as defined by gene expression and that these signatures are similarly correlated in NSCLC cell lines and tumors. We identify multiple DMRs, including ERBB2 and ZEB2, whose methylation status is strongly associated with an epithelial phenotype in NSCLC cell lines, surgically resected tumors, and formalin-fixed biopsies from NSCLC patients who went on to fail front-line chemotherapy. CONCLUSIONS: Our data demonstrate that patterns of DNA methylation can divide NSCLCs into two phenotypically distinct subtypes of tumors and provide proof of principle that differences in DNA methylation can be used for predictive biomarker discovery and development. To determine whether phenotypic subsets of NSCLC can be defined based on their DNA methylation patterns, we combined microfluidics-based gene expression analysis and genome-wide methylation profiling. We derived robust classifiers for both gene expression and methylation in cell lines and tested these classifiers in surgically resected NSCLC tumors. We validate our approach using quantitative RT-PCR and methylation specific PCR in formalin-fixed biopsies from NSCLC patients who went on to fail front-line chemotherapy.
2012-03-03 | E-GEOD-36216 | biostudies-arrayexpress
Project description:TGFBR2 was deleted in ovarian cancer TIL via CRISPR/Cas9 gene editing. Response of unmodified and TGFBR2 knockout TIL to TGF-B stimulation was evaluated via RNA sequencing.
2022-08-03 | GSE169659 | GEO
Project description:Many studies have shown association of tumor infiltrating B-cells and presence of tertiary lymphoid structure with improved clinical responses to immune checkpoint inhibitors therapy. We hypothesized that their presence could also have an impact on TIL therapy response. To address this, we performed RNA-seq of FFPE samples from a cohort of patients that received TIL therapy. Melanoma tumors collected prior to TIL infusion were evaluated for immune content in 9 responders and 11 non-responders to TIL therapy. Our data demonstrate an increase in class-switched memory B-cells in responders compared with non-responders to TIL therapy. In the myeloid compartment, increased presence of dendritic cell populations (pDC, aDC, and iDC) and basophils was observed in responders to TIL therapy, as well as higher content of γδ T cells and effector memory CD8+ T cells (CD8+ Tem) in the T-cell compartment. Next, we assessed the TLS presence in the same cohort by a gene expression signature of 12 chemokines using principal component analysis. The responders showed a higher TLS score compared with the non-responder patients, suggesting that patients responding to TIL therapy had more TLS in their tumors than the non-responder patients. These observations indicate that, same as in the immune checkpoint inhibitors therapy response, presence of B-cells and TLS might have a positive impact in the clinical outcome to TIL therapy.
2024-06-30 | GSE217387 | GEO
Project description:Regulatory T cells (Treg) are conventionally viewed to suppress endogenous and therapy-induced anti-tumor immunity; however, their role in modulating responses to immune checkpoint blockade (ICB) is unclear. In this study, we integrated single-cell RNAseq/TCRseq of >73,000 tumor-infiltrating Treg (TIL-Treg) from anti-PD-1-treated and treatment naive non-small cell lung cancers (NSCLC) with single cell analysis of tumor-associated antigen (TAA)-specific Treg derived from a murine tumor model. We identified 10 subsets of human TIL-Treg, most of which have high concordance with murine TIL-Treg subsets. Notably, only one subset selectively expresses high levels of OX40 and GITR, whose engangement by cognate ligand mediated proliferative programs and NF-kB activation, as well as multiple genes involved in Treg suppression, including LAG3. Functionally, the OX40hiGITRhi subset is the most highly suppressive ex vivo and its higher representation among total TIL-Treg correlated with resistance to PD-1 blockade. Surprisingly, in the murine tumor model, we found that virtually all TIL-Treg expressing T cell receptors that are specific for TAA fully develop a distinct Th1-like signature over a two-week period after entry into the tumor, down-regulating FoxP3 and up-regulating expression of TBX21 (Tbet), IFN and certain pro-inflammatory granzymes. Transfer learning of a gene score from the murine TAA-specific Th1-like Treg subset to the human single-cell dataset revealed a highly analogous subcluster that was enriched in anti-PD-1 responding tumors. These findings demonstrate that TIL-Treg partition into multiple distinct transcriptionally-defined subsets with potentially opposing effects on ICB-induced anti-tumor immunity and suggest that TAA-specific TIL-Treg may positively contribute to anti-tumor responses.
2023-09-11 | GSE235602 | GEO
Project description:Regulatory T cells (Treg) are conventionally viewed to suppress endogenous and therapy-induced anti-tumor immunity; however, their role in modulating responses to immune checkpoint blockade (ICB) is unclear. In this study, we integrated single-cell RNAseq/TCRseq of >73,000 tumor-infiltrating Treg (TIL-Treg) from anti-PD-1-treated and treatment naive non-small cell lung cancers (NSCLC) with single cell analysis of tumor-associated antigen (TAA)-specific Treg derived from a murine tumor model. We identified 10 subsets of human TIL-Treg, most of which have high concordance with murine TIL-Treg subsets. Notably, only one subset selectively expresses high levels of OX40 and GITR, whose engangement by cognate ligand mediated proliferative programs and NF-kB activation, as well as multiple genes involved in Treg suppression, including LAG3. Functionally, the OX40hiGITRhi subset is the most highly suppressive ex vivo and its higher representation among total TIL-Treg correlated with resistance to PD-1 blockade. Surprisingly, in the murine tumor model, we found that virtually all TIL-Treg expressing T cell receptors that are specific for TAA fully develop a distinct Th1-like signature over a two-week period after entry into the tumor, down-regulating FoxP3 and up-regulating expression of TBX21 (Tbet), IFN and certain pro-inflammatory granzymes. Transfer learning of a gene score from the murine TAA-specific Th1-like Treg subset to the human single-cell dataset revealed a highly analogous subcluster that was enriched in anti-PD-1 responding tumors. These findings demonstrate that TIL-Treg partition into multiple distinct transcriptionally-defined subsets with potentially opposing effects on ICB-induced anti-tumor immunity and suggest that TAA-specific TIL-Treg may positively contribute to anti-tumor responses.
2023-09-11 | GSE235500 | GEO