Reprogramming of Tumor-infiltrating Immune Cells in Early Stage of NSCLC
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA482529 | ENA |
REPOSITORIES: ENA
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Project description:Comparing the relative proportions of immune cells in tumor and adjacent normal tissue from NSCLC patients demonstrates the early changes of tumor immunity and provides insights to guide immunotherapy design. We mapped the immune ecosystem using computational deconvolution of bulk transcriptome data from the Cancer Genome Atlas (TCGA) and single cell RNA sequencing (scRNA-seq) data of dissociated tumors from early-stage non-small cell lung cancer (NSCLC) to investigate early immune landscape changes occurring during tumorigenesis. Computational deconvolution of immune infiltrates in 44 NSCLC and matching adjacent normal samples from TCGA showed heterogeneous patterns of alterations in immune cells. The scRNA-seq analyses of 11,485 cells from 4 treatment-naïve NSCLC patients comparing tumor to adjacent normal tissues showed diverse changes of immune cell compositions. Notably, CD8+ T cells and NK cells are present at low levels in adjacent normal tissues, and are further decreased within tumors. Myeloid cells exhibited marked dynamic reprogramming activities, which were delineated with differentiation paths through trajectory analysis. A common differentiation path from CD14+ monocytes to M2 macrophages was identified among the 4 cases, accompanied by up-regulated genes (e.g. ALCAM/CD166, CD59, IL13RA1, IL7R) with enriched functions (adipogenesis, lysosome), and down-regulated genes (e.g. CXCL2, IL1B, IL6R) with enriched functions (TNFa signaling via NF-kB, inflammatory response). Computational deconvolution and single cell sequencing analyses have revealed a highly dynamic immune reprogramming that occurs in early stage NSCLC development, suggesting that normalizing both immune compartments may represent a viable strategy for treatment of early stage cancer and prevention of progression.
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Project description:Gene expression profiling of NSCLC tissues let to the establishment of several prognostic, predictive gene signatures with little overlap. To study factors introducing variability into gene expression microarray studies we compared interpatient (patient-to-patient) and intrapatient (tumor sub-sample) variations in gene expression profiles in stage I and II NSCLC tissues. We identified 128 probe sets which showed variable intratumoral expression Four different sites (A,B,C,D) of individual primary tumors and matched distant normal lung tissue (N) from 20 patients were used to establish gene expression patterns captured by Affymetrix HG-U133 Plus 2.0 arrays (n = 100).
2014-09-23 | E-GEOD-33532 | biostudies-arrayexpress
Project description:We identified a tumor signature of 5 genes that aggregates the 156 tumor and normal samples into the expected groups. We also identified a histology signature of 75 genes, which classifies the samples in the major histological subtypes of NSCLC. A prognostic signature of 17 genes showed the best association with post-surgery survival time. The performance of the signatures was validated using a patient cohort of similar size A genome-wide gene expression analysis was performed on a cohort of 91 patients. We used 91 tumor- and 65 adjacent normal lung tissue samples. We defined sets of predictor genes (probe sets) with the expression profiles. The power of predictor genes was evaluated using an independent cohort of 96 non-small cell lung cancer- and 6 normal lung samples
2010-05-28 | E-GEOD-19188 | biostudies-arrayexpress
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2014-07-29 | E-MTAB-1790 | biostudies-arrayexpress
Project description:Exon Level Expression Profiling analysis of early stage NSCLC suffering rapidly relapse
| PRJNA498619 | ENA
Project description:<p><strong>OBJECTIVES:</strong> High activity of Indoleamine 2,3-dioxygenase1 (IDO1) in lung cancer patients converts tryptophan (Trp), which is the essential amino acid for T cell metabolism, to kynurenine (Kyn) and consequently suppresses anti-tumor immune responses. We aimed to track the dynamics of IDO1 activity in stage III non-small cell lung cancer (NSCLC) patients who received first-line radiotherapy (RT) and explore its association with survival outcomes.</p><p><strong>MATERIALS AND METHODS:</strong> Systemic IDO1 activity was calculated by Kyn:Trp ratio. Plasma levels of Kyn and Trp in 113 thoracic RT-received stage III NSCLC patients were measured by high-performance liquid chromatography before the initiation of RT. Dynamic change of IDO1 activity was followed in 24 patients by measuring Kyn:Trp ratio before, during and after RT administration.</p><p><strong>RESULTS:</strong> In 24 patients with dynamic tracking of plasma IDO1 activity, there was no significant alterations observed among the 3 time points (Friedman test, p=0.13). The changing pattern of Kyn:Trp ratio was divided into 4 groups: decreased consistently during RT, first increased then decreased, increased consistently, first decreased then increased. Patients whose Kyn:Trp ratio kept decreasing or first increased then decreased were defined as good-change group. The good-change status was identified as an independent positive factor for overall survival (OS) and progression-free survival (PFS) (p=0.04; p=0.01) in multivariate analysis among evaluated parameters. Patients with good change showed significantly superior local control than bad-change group (p=0.01, HR=0.22). In 113 stage III NSCLC patients with pre-radiation Kyn:Trp ratio, a trend that high baseline IDO1 activity was associated with short OS was observed (p=0.079).</p><p><strong>CONCLUSION: </strong>Favorable change of IDO1 activity during RT was associated with superior OS, PFS and local control. IDO1 activity is a promising biomarker for prognosis in stage III NSCLC patients.</p>
2022-08-05 | MTBLS5267 | MetaboLights