Spatio-temporal mapping of immune cell dynamics during human sequential lymph node metastasis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE328422 | GEO | 2026/06/27
REPOSITORIES: GEO
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| GSE328422_TNBC_sequential_LN_metastasis_Xenium_Seurat_object.rds | Other |
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Project description:Regional lymph node metastasis critically influences distant metastatic progression, anti-tumor immunity, and patient prognosis in triple-negative breast cancer (TNBC). In this study, fresh surgically resected specimens from treatment-naive TNBC patients were collected and CD45+ immune cells were isolated for single-cell RNA sequencing to characterize immune remodeling across matched primary tumors, sentinel tumor-draining lymph nodes (S-TDLNs), and secondary axillary lymph nodes (ALNs). The overall project integrated scRNA-seq with imaging mass cytometry, Visium and Xenium spatial transcriptomics, and multiplex immunofluorescence. This GEO submission contains processed scRNA-seq expression matrices and associated metadata only. Raw sequencing data have been deposited previously in in the Genome Sequence Archive (GSA) for human data, and the GSA ID is HRA010347.
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Project description:Current cancer immunotherapies can induce tumour regression, although responses are often not durable. Recent studies have highlighted the importance of enforcing a systemic immune response from tumour-draining lymph nodes (TDLNs). However, mechanisms driving immune suppression in TDLNs remain poorly studied. We applied spatial proteogenomics on melanoma TDLNs and identified regional differences in immune cell composition in lymph nodes from patients with long-term (>5 years) disease control compared to those with early (<2 years) disease recurrence. TDLNs from patients with a poor prognosis were characterized by the expansion of regulatory T cells (Tregs), dendritic cells (DCs), and macrophages interacting with cytotoxic CD8+ T cells. Targeted transcriptomics of cell types within this spatial neighbourhood revealed immunoregulatory myeloid cell phenotypes engaging with CD8+ T cells poised for exhaustion. Besides known immune-suppressive molecules such as IDO and PD-L1, paracortex macrophages and DCs in patients with recurrent disease expressed high levels of the secreted phospholipase PLA2G2D across different cancer types. Additionally, PLA2G2D was upregulated in non-small cell lung cancer patients who developed acquired resistance to anti-PD-1 immunotherapy. Importantly, PLA2G2D loss-of-function or therapeutic inhibition markedly improved survival in tumour-bearing mice and increased the efficacy of anti-PD-1 immunotherapy. Collectively, we show that in-depth spatial profiling of cancer patient TDLNs offers novel insights into systemic anti-tumour immunity and identifies PLA2G2D as a target for cancer immunotherapy.
2026-06-23 | GSE333464 | GEO
Project description:Background: Cervical lymph node metastasis is a potent prognostic factor in oral squamous cell carcinoma (OSCC). However, lymph nodes resected by sentinel node biopsy or neck dissection are usually diagnosed by examining only one or two sections of the maximal cut surface. Accurate diagnosis of the metastasis in lymph nodes is important but depends on a heavy workload of the pathologist. In this study, we have attempted to identify novel molecular markers to find the harboring cancer cells in the lymph node and establish rapid detection method. Methods: We determined the gene expression profiles of 7 metastatic lymph nodes from patients with OSCC and 1 normal lymph node and 5 salivary glands from non-cancerous patients by microarray analysis. We found the overexpression genes in all metastatic lymph nodes. Subsequently, we examined the expression of these genes in newly 23 metastatic lymph nodes and 9 normal lymph nodes by real-time quantitative RT-PCR (qRT-PCR) assay. Moreover, the rapid detection of lymph node metastasis by these genes was examined using the reverse transcription loop-mediated isothermal amplification (RT-LAMP) method. Result: Among the 4 genes identified by microarray analysis, annexin A8 (ANXA8) and desmoglein 3 (DSG3) were detected in all metastatic lymph nodes at a much higher level but not in normal lymph nodes at all by qRT-PCR. Furthermore, RT-LAMP method targeting ANXA8 rapidly detected almost lymph nodes with metastasis. Conclusions: ANXA8 could be a useful marker for detecting lymph node metastasis in OSCC. Using AB1700 system, we determined the gene expression profiles of lymph nodes with metastasis of OSCC. Normal lymph node and salivary gland tissues were used as control samples.
2015-12-21 | E-GEOD-70604 | biostudies-arrayexpress
Project description:Background: Cervical lymph node metastasis is a potent prognostic factor in oral squamous cell carcinoma (OSCC). However, lymph nodes resected by sentinel node biopsy or neck dissection are usually diagnosed by examining only one or two sections of the maximal cut surface. Accurate diagnosis of the metastasis in lymph nodes is important but depends on a heavy workload of the pathologist. In this study, we have attempted to identify novel molecular markers to find the harboring cancer cells in the lymph node and establish rapid detection method. Methods: We determined the gene expression profiles of 7 metastatic lymph nodes from patients with OSCC and 1 normal lymph node and 5 salivary glands from non-cancerous patients by microarray analysis. We found the overexpression genes in all metastatic lymph nodes. Subsequently, we examined the expression of these genes in newly 23 metastatic lymph nodes and 9 normal lymph nodes by real-time quantitative RT-PCR (qRT-PCR) assay. Moreover, the rapid detection of lymph node metastasis by these genes was examined using the reverse transcription loop-mediated isothermal amplification (RT-LAMP) method. Result: Among the 4 genes identified by microarray analysis, annexin A8 (ANXA8) and desmoglein 3 (DSG3) were detected in all metastatic lymph nodes at a much higher level but not in normal lymph nodes at all by qRT-PCR. Furthermore, RT-LAMP method targeting ANXA8 rapidly detected almost lymph nodes with metastasis. Conclusions: ANXA8 could be a useful marker for detecting lymph node metastasis in OSCC.
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Project description:Background Breast cancer patients who present in the early stage of disease are affected by metastasis to the axillary group of lymph nodes. The first among this group that is affected is called as sentinel lymph node, and metastasis to this lymph node is crucial for the staging of cancer and the quality of surgical intervention. Sentinel Lymph Node Biopsy (SLNB) that is currently used to assess lymph node metastasis is neither sensitive, nor specific, is time-consuming, thereby necessitating the identification of novel biomarkers that can flag sentinel lymph node metastasis. Methods Breast cancer patients were screened, and those with early stage were recruited in the study. Surgical resection of the breast was followed by identification of sentinel lymph nodes by methylene fluorescent technique. Histo-pathology of fresh frozen section biopsy was used as the gold standard to assign the clinical phenotypes of metastatic (SLNM+) and non-metastatic sentinel lymph nodes (SLNM-). Discovery phase of the experiment included isobaric Tags for Relative and Absolute Quantitation (iTRAQ) technique comprising of six comparative experiments coupled with mass spectrometric analysis on Orbitrap Fusion to identify differentially expressed proteins on Proteome Discoverer 2.4. Functional enrichment and pathway analyses of differentially regulated genes was carried out in DAVID functional annotation tool. Validation was done by ELISA and protein concentrations were used to estimate the ROC for computing diagnostic parameters. Results Based on MS/MS spectra there were 2396 unique protein groups and 81 differentially expressed proteins comparing SLNB + and SLNB -. Nineteen proteins up-regulated, and eight proteins that were down regulated in SLNB+ as compared to SLNB-. Bioinformatic analysis showed the implication of extra cellular matrix proteins and ECM-receptor interaction pathways to be implicated in lymph node metastasis. ELISA confirmed the up-regulation of caveolin 1, collagen α-1, desmin, fibrillin-1, and microfibrillar associated glycoprotein 4 in metastatic, as compared to non-metastatic lymph nodes. These proteins are known to be integral in tumorogenesis, cell proliferation, invasion, cell survival and anti-apoptosis. These proteins have 80%-100%, of sensitivity and specificity to differentiate the two clinical phenotypes. Conclusion Identified extra cellular matrix protein biomarkers have requisite diagnostic parameters to be developed as a translational tool to assess the status of sentinel lymph nodes during mastectomy procedure to guide surgical therapy of axillary lymph nodes in early breast oncology.
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2018-10-26 | PXD005539 | Pride