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Spatial Immune Associations of Immunotherapy Response in Non-Small Cell Lung Cancer by Multiplexed Tissue Imaging
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raw data related to project "Circulating biomarkers as predictors of gender-specific response to Immune Checkpoint Inhibitors in melanoma and non-small-cell lung cancer patients"
<p><strong>Sex-related differences in serum biomarker levels predict the activity and efficacy of Immune Checkpoint Inhibitors in advanced melanoma and Non-Small Cell Lung Cancer patients.</strong></p> <p><strong>Abstract </strong></p> <p><strong>Background:</strong> Immune Checkpoint Inhibitors (ICIs) lead to durable response and a significant increase in long-term survival in patients with advanced malignant melanoma (MM) and Non-Small Cell Lung Cancer (NSCLC). The identification of serum cytokines that can predict their activity and efficacy, and their sex interaction, could improve treatment personalization. </p> <p><strong>Methods: </strong>In this prospective study, we enrolled immunotherapy-naïve patients affected by advanced MM and NSCLC treated with ICIs. The primary endpoint was to dissect the potential sex correlations between serum cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, GM-CSF, MCP-1, TNF-ɑ, IP-10, VEGF, sPD-L1) and the overall response rate (ORR). Secondly, we analyzed biomarker changes during treatment related to ORR, disease control rate (DCR), progression free survival (PFS) and overall survival (OS). Blood samples, collected at baseline and during treatment until disease progression (PD) or up to 2 years, were analyzed using Luminex xMAP or ELLA based technology. </p> <p>Three Luminex xMAP assays and two ELLA microfluidic cartridges were used to screen 28 immune-related biomarkers in 38 paired serum and citrate-theophylline-adenosine-dipyridamole (CTAD) plasma samples collected from 10 advanced melanoma or non-small cell lung cancer (NSCLC) patients at different time points during immunotherapy.</p> <p><strong>Results</strong>: Serum samples from 161 patients (98 males/63 females; 92 MM/69 NSCLC) were analyzed for treatment response. At baseline, IL-6 was significantly lower in females (F) <em>versus</em> males (M); lower levels of IL-4 in F and of IL-6 in both sexes significantly correlated with a better ORR, while higher IL-4 and TNF-ɑ values were predictive of a lower probability of ORR in F <em>versus</em> M. One hundred and sixty-five patients were evaluable for survival analysis: at multiple Cox regression, an increased risk of PD was observed in F with higher baseline values of IL-4, sPD-L1 and IL-10, while higher IL-6 was a negative predictor in males. In males, higher levels of GM-CSF predict a longer survival, whereas higher IL-1β predicts a shorter survival. Regardless of sex, high baseline IL-8 values were associated with an increased risk of both PD and death, and high IL-6 levels only with shorter OS. </p> <p>Twenty-three of 28 biomarkers were detected both in serum and plasma by at least one of the assays, including IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, GM-CSF, IFN-γ, TNF-α, VEGF, IP-10, MCP-1, eotaxin, fractalkine, G-CSF, IFN-α, IL-1RA, IL-13, IL-17A, MIP-1β and sPD-L1. Conversely, FGF-2 and IL-1α were not detected in both matrices; GRO-α factor and EGF were detected only in serum and MIP-1α only in plasma. sPD-L1, MCP-1, IFN-γ, IL-8, MIP-1β and VEGF were, respectively, 1.15-, 1.44-, 1.83-, 2.43-, 2.82-, 6.72-fold higher in serum, whereas IL-10, IL-4, IL-2 and IL-5 were 1.05-, 1.19-, 1.92- and 2.17-fold higher, respectively, in plasma. IP-10 levels were higher in plasma but, as well as for VEGF, the bias serum versus plasma varied depending on the assay used (IP-10: −5.7% to −145%; VEGF: 115% to 165%). No significant differences were found for the remaining nine analyzed cytokines.</p> <p><strong>Conclusions</strong></p> <p>Serum IL-1β, IL-4, IL-6, IL-10, GM-CSF, TNFɑ, and sPDL1 had a significant independent sex-related predictive impact on ORR, PFS and OS in melanoma and NSCLC patients treated with ICIs. These results will potentially pave the way for new ICI combinations, designed according to baseline and early changes of these cytokines and stratified by sex. </p> <p>The cytokine and sPD-L1 levels may differ between serum and plasma samples collected from cancer patients treated with immunotherapy, and the results obtained can be influenced by the different characteristics of the tested assays.</p>
Basil-Mediated Synthesized Manganese Oxide Nanoparticles: Antioxidant, Anti-Inflammatory and Cytotoxic Activities on MCF-7 Cancer Cell Line
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Mapping spatial organization and genetic cell state regulators to target immune evasion in ovarian cancer
<p>This collection of data accompanies the study: <a href="https://www.nature.com/articles/s41590-024-01943-5">Yeh, Aguirre, Laveroni <em>et al.</em> <strong>Mapping spatial organization and genetic cell-state regulators to target immune evasion in ovarian cancer. </strong>(2024). </a><em><strong><a href="https://www.nature.com/articles/s41590-024-01943-5">Nature Immunology</a>.</strong></em> Files are provided in the form of RObjects (extension .rds) or tabulated data (extension .csv) to reproduce the results and figures provided in the paper via the the R programming environment using Code provided <a href="https://github.com/Jerby-Lab/HGSC_SpatialPerturbational">here</a>. </p> <p> </p> <p>Data collected and processed and published as a part of this study of tubo-ovarian high grade serous carcinoma (HGSC) includes: </p> <ul> <li>~<strong>2.5 million single cell spatial transcriptomics profiles</strong> from <strong>130 HGSC tumors</strong> of <strong>94 patients</strong></li> <li>Matching de-identified <strong>clinical annotations</strong> and clinical outcomes.</li> <li>Matching <strong>targeted genomic data</strong> from the bulk tumor tissues.</li> <li><strong>Perturb-seq CRISPR knockout</strong> data in ovarian cancer cells in monoculture and co-culture with Natural Killer (NK) cells.</li> </ul> <p>The spatial transcriptomics, Perturb-Seq, and matched H&E (Hematoxylin & Eosin, where available) are also provided via the Single Cell Portal with an <strong>interactive interface</strong> (<a href="https://singlecell.broadinstitute.org/single_cell/study/SCP2640/hgsc-spatial-cohort-discovery-dataset">SCP2640</a>, <a href="https://singlecell.broadinstitute.org/single_cell/study/SCP2641/hgsc-spatial-cohort-validation-1-dataset">SCP2641</a>, <a href="https://singlecell.broadinstitute.org/single_cell/study/SCP2650/hgsc-spatial-cohort-validation-2-dataset">SCP2650</a>, <a href="https://singlecell.broadinstitute.org/single_cell/study/SCP2644/hgsc-spatial-cohort-test-1-dataset">SCP2644</a>, <a href="https://singlecell.broadinstitute.org/single_cell/study/SCP2646/hgsc-spatial-cohort-test-2-dataset">SCP2646</a>, <a href="https://singlecell.broadinstitute.org/single_cell/study/SCP2707/hgsc-spatial-study-perturb-seq">SCP2707</a>).</p> <p>The collection also includes previously published data that was analyzed and used in this study to examine the generalizability of the findings, evaluate immunotherapy predictors, and for data-driven experimental design.</p> <p>The SeuratObj.zip contains six SeuratObjects matching the five spatial transcriptomcs datasets (Discovery, Validation 1, Validation 2, Test 1 and Test 2) and Perturb-Seq data.</p> <p>The Yeh2024.zip file includes the study's data and additional datasets/results to reproduce the study's figures. A detailed description of the files included in the repository is provided in `README.txt` and `README.xlsx`</p>
An isoform-resolution transcriptomic atlas of colorectal cancer from long-read single-cell sequencing
<p>Relavant codes and notebooks for data analysis: <a href="https://github.com/lzx325/CRC-atlas">https://github.com/lzx325/CRC-atlas</a></p>
Fig. 7 in Phytoconstituents from Vernonia glaberrima Welw. Ex O. Hoffm. leaves and their cytotoxic activities on a panel of human cancer cell lines
Fig. 7. Surface structure of CDK2 (PDB ID 2DUV) showing the binding pose of lupeol (black). Blue colour depicts polar surface while brown colour indicates hydrophobic surfaces. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Fig. 5. MCF-7 in Ethanolic extract of Mimosa caesalpiniifolia leaves: Chemical characterization and cytotoxic effect on human breast cancer MCF-7 cell line
Fig. 5. MCF-7 cell colony diameter (μm) after treatment with cyclophosphamide (CP, 550 μg/mL) and different concentrations (5.0–320.0 μg/mL) of the ethanolic extract of Mimosa caesalpiniifolia leaves (EEM) for 24 or 48 h, compared to the negative control cells (NC). Results are expressed as mean ± SEM of three independent experiments. Different letters indicate significant differences (p <0.01) by the Tukey test. Note cell colony-diameter reduction after treatment, in comparison to the negative control cells, thereby indicating EEM cytotoxicity.
Fig. 5 in Phytoconstituents from Vernonia glaberrima Welw. Ex O. Hoffm. leaves and their cytotoxic activities on a panel of human cancer cell lines
Fig. 5. Effects of V. glaberrima compounds on the viability of HT-29 cell lines as determined by MTS assay.
Table 4 in Phytoconstituents from Vernonia glaberrima Welw. Ex O. Hoffm. leaves and their cytotoxic activities on a panel of human cancer cell lines
<p><b>Table 4</b> Docking scores of 5-methylcoumarin-4-β- glucoside and 4-hydroxy-5-methylcoumarin on carbonic anhydrase IX (CAIX) (PDB ID 3IAI).</p><table><tbody><tr><th></th><th>Name</th><th>Free binding energy (kcal/mol)</th><th>Estimated inhibition constant (Ki)</th></tr></tbody><tbody><tr><th>1</th><td>5-Methylcoumarin-4-β- glucoside</td><td><i>−</i> 6.97</td><td>7.78 μM</td></tr><tr><th>2</th><td>4-Hydroxy-5-methylcoumarin</td><td><i>−</i> 5.70</td><td>66.17 μM</td></tr><tr><th>3</th><td>Co-crystallized ligand</td><td><i>−</i> 6.01</td><td>39.32 μM</td></tr></tbody></table>
Table 3 in Phytoconstituents from Vernonia glaberrima Welw. Ex O. Hoffm. leaves and their cytotoxic activities on a panel of human cancer cell lines
<p><b>Table 3</b> Docking result for lupeol on CDK2 (PDB ID 2DUV).</p><table><tbody><tr><th></th><th>Name</th><th>Free binding energy (kcal/mol)</th><th>Estimated inhibition constant (Ki)</th></tr></tbody><tbody><tr><th>1</th><td>Lupeol</td><td><i>−</i> 11.06</td><td>7.82 nM</td></tr><tr><th>2</th><td>Co-crystallized</td><td><i>−</i> 11.08</td><td>7.57 nM</td></tr></tbody></table>
Cancer Genome Study Using Samples From Patients With Stage I or Stage II Non-Small Cell Lung Cancer Treated on Clinical Trial ACOSOG-Z0030
ClinicalTrials.gov study NCT00899535. IPD Sharing: Not stated. Countries: 0. Publications: 0.
Minimal Residual Disease Dynamic Monitoring in First-Line Serplulimab Plus Chemotherapy in Treatment of Extensive Small Cell Lung Cancer: An Observational Study
ClinicalTrials.gov study NCT05873790. IPD Sharing: NO. Countries: 0. Publications: 0.
Temozolomide Combine With Intensity Modulated Radiation Therapy With Simultaneous Integrated Boost for Non Small Cell Lung Cancer Brain Metastases
ClinicalTrials.gov study NCT03732482. IPD Sharing: Not stated. Countries: 0. Publications: 0.
Identification of Novel Biomarkers of Response to Systemic Treatments in Renal Cell Cancer
ClinicalTrials.gov study NCT04060537. IPD Sharing: UNDECIDED. Countries: 0. Publications: 0.
Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Sunitinib as First-Line Therapy in Treating Patients With Stage IV Non-Small Cell Lung Cancer
ClinicalTrials.gov study NCT00748163. IPD Sharing: Not stated. Countries: 0. Publications: 0.
A Study Comparing Ensatinib Versus Platinum-Based Chemotherapy as Adjuvant Treatment for Stage II-IIIA ALK -Positive Non-Small Cell Lung Cancer
ClinicalTrials.gov study NCT05186506. IPD Sharing: NO. Countries: 0. Publications: 0.
Immunomagnetic Detection of Cancer Cells in Pleural Effusion in Lung Cancer Patients as Additional Staging and Prognostic Tool
ClinicalTrials.gov study NCT02172027. IPD Sharing: Not stated. Countries: 0. Publications: 0.
Tarceva and AT-101 for Patients With Advanced Non-Small Cell Lung Cancer
ClinicalTrials.gov study NCT00934076. IPD Sharing: Not stated. Countries: 0. Publications: 0.
Efficacy Study of Induction Chemotherapy Before Surgery in Operable Non-small Cell Lung Cancer
ClinicalTrials.gov study NCT00329472. IPD Sharing: Not stated. Countries: 0. Publications: 0.
Rociletinib Genomic Landscape in Non-small Cell Lung Cancer (NSCLC)
ClinicalTrials.gov study NCT02705339. IPD Sharing: NO. Countries: 0. Publications: 0.
ScienceDex guides
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These curated guides explain access requirements, typical timelines, costs, and reuse considerations for widely used research datasets.
Allen Brain Atlas
Allen Brain Atlas is an Allen Institute collection of brain map atlases, datasets, APIs, and analysis tools covering mouse, human, and non-human primate brain resources.
Annotated Behaviour and Observability Dataset (ABODe)
ABODe is a University of Edinburgh DataShare dataset for behavior classification in group-housed mice using home-cage video, identities, bounding boxes, ground-plate positions, and annotator labels.
DANDI Archive for NWB datasets
DANDI is a BRAIN Initiative archive for publishing and sharing neurophysiology data, including electrophysiology, optophysiology, and behavioral data packaged as NWB and related standards.
International Brain Laboratory public data
The International Brain Laboratory public data releases expose standardized mouse decision-making experiments, including Neuropixels recordings, widefield calcium imaging, behavior, and session metadata accessed through the ONE API.
OpenNeuro
OpenNeuro is a free, open platform for sharing neuroimaging datasets, with public search, dataset pages, and download paths for web, S3, DataLad, and the OpenNeuro CLI.