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Human Early Postnatal Thymus [CITE-seq]

ABSTRACT: Within the thymus, regulation of the cellular cross-talk directing T cell development is dependent on spatial interactions within specialized niches. To create a holistic, spatially defined map of tissue niches guiding postnatal T cell development we employed the multidimensional imaging platform CO-detection by indEXing (CODEX), as well as Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) and Assay for Transposable-Accessible Chromatin (ATAC-seq). We generated age-matched 4–5-month-old postnatal thymus datasets for both male and female donors, and describe signaling and cell-cell interaction networks in sequential thymocyte developmental niches. Together, these data represent a unique age-matched spatial multiomic resource to investigate how sex-based differences in thymus regulation and T cell development arise, and provide an essential resource to understand the mechanisms underlying immune function and dysfunction in males and females.

ORGANISM(S): Homo sapiens

PROVIDER: GSE264587 | GEO | 2024/08/30

REPOSITORIES: GEO

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Project description:Background: A pressing challenge in treating non-small cell lung cancer (NSCLC) lies in the significant variability of patient responses to immunotherapy. This issue underscores the critical need for innovative predictive models that can navigate beyond conventional biomarkers to enhance patient outcomes, particularly by addressing immunotherapy resistance or responsiveness. Hypothesis: We hypothesize that an integrated multi-omics approach will uncover interactions within the NSCLC tumor immune microenvironment (TIME) and identify novel biomarkers that are predictive of individual immunotherapy responses, thus aiding in the development of a robust personalized treatment planning model. Objective: To develop a predictive model for NSCLC immunotherapy response/resistance by identifying new biomarkers using co-detection by indexing (CODEX) and Digital Spatial Profiling of whole transcriptome atlas (DSP-WTA). Methods: We utilized a multi-omics approach, combining CODEX for spatial mapping of protein expression at the single-cell level and DSP-WTA for comprehensive transcriptomic insights from the cell types identified by CODEX. This methodology facilitated a detailed examination of the TIME in NSCLC samples from patients undergoing first-line immunotherapy. Results: Our analysis identified three cell types, proliferating tumor cells, granulocytes, and vessels, that are associated with resistance to immunotherapy. The high proportion of these cell types demonstrated a hazard ratio (HR) of 3.8 (p = 0.004) in the training cohort (N = 33) and 1.8 (p = 0.05) in the validation cohort (N = 35). In the response cell type model, higher levels of M1 macrophages, M2 macrophages, and CD4 T cells returned a HR of 0.4 (p = 0.019) in the training set and 0.49 (p = 0.036) in the validation set. Gene signatures related to these cell types also predicted outcomes with high accuracy. The resistant gene model, which included 8 genes associated with epithelial-mesenchymal transition (EMT) and cell migration showed a HR of 5.3 (p < 0.001) in the training set and 2.2 (p = 0.036) in the validation set. The response gene model, consisting of 8 genes associated with immunomodulation, had an HR of 0.22 (p = 0.005) in the training set and 0.38 (p = 0.034) in the validation set. Conclusion: This research highlights the potential of a multi-omics strategy in advancing NSCLC treatment toward precision oncology. By offering insights into the TIME and unveiling novel biomarkers, our model seeks to define resistance and to improve prediction of response to treatment.

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Human Early Postnatal Thymus [CITE-seq]

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