Summary of Study ST003286

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002038. The data can be accessed directly via it's Project DOI: 10.21228/M85V5Z This work is supported by NIH grant, U2C- DK119886.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST003286
Study TitleInteraction between NSCLC cells, CD8+ T cells and immune checkpoint inhibitors potentiates coagulation and promotes metabolic remodeling- new cues on CAT-VTE
Study SummaryCancer-related thrombosis (CAT) and venous thromboembolism (VTE) are common cancer-related sequelae linked with high mortality, therefore finding predictive indicators is critical. Immune checkpoint inhibitors (ICI) are utilized in cancer immunotherapy to activate T lymphocytes against cancer cells. Recent retrospective investigations found that some individuals experienced increased VTE after receiving ICI. We postulated that ICI (anti-CTLA4 and anti-PD1) effect on immunological and cancer cells, as well as their interaction, contributes for an elevated risk of CAT-VTE. Our objective is to investigate this molecular interaction in order to uncover potential prothrombotic indicators. We pharmacologically modulated non-small cell lung cancer (NSCLC) cell lines in co-culture with CD8+ T lymphocytes (T CD8+) obtained from healthy blood donors. Nuclear Magnetic Resonance (NMR) metabolic remodeling analysis revealed differences in extracellular metabolite concentrations after T CD8+ and ICI treatment.
Institute
ITQB NOVA
Last NameGonçalves
First NameLuís
AddressAvenida Republica
Emaillgafeira@itqb.unl.pt
Phone214469464
Submit Date2023-11-20
Raw Data AvailableYes
Raw Data File Type(s)fid
Analysis Type DetailNMR
Release Date2024-07-03
Release Version1
Luís Gonçalves Luís Gonçalves
https://dx.doi.org/10.21228/M85V5Z
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Project:

Project ID:PR002038
Project DOI:doi: 10.21228/M85V5Z
Project Title:Interaction between NSCLC cells, CD8+ T cells and immune checkpoint inhibitors potentiates coagulation and promotes metabolic remodeling- new cues on CAT-VTE
Project Summary:Abstract Cancer-related thrombosis (CAT) and venous thromboembolism (VTE) are common cancer-related sequelae linked with high mortality, therefore finding predictive indicators is critical. Immune checkpoint inhibitors (ICI) are utilized in cancer immunotherapy to activate T lymphocytes against cancer cells. Recent retrospective investigations found that some individuals experienced increased VTE after receiving ICI. We postulated that ICI (anti-CTLA4 and anti-PD1) effect on immunological and cancer cells, as well as their interaction, contributes for an elevated risk of CAT-VTE. Our objective is to investigate this molecular interaction in order to uncover potential prothrombotic indicators. We pharmacologically modulated non-small cell lung cancer (NSCLC) cell lines in co-culture with CD8+ T lymphocytes (T CD8+) obtained from healthy blood donors. Nuclear Magnetic Resonance (NMR) metabolic remodeling analysis revealed differences in extracellular metabolite concentrations after T CD8+ and ICI treatment.
Institute:ITQB NOVA
Last Name:Gonçalves
First Name:Luís
Address:Avenida Republica
Email:lgafeira@itqb.unl.pt
Phone:00351 214469464

Subject:

Subject ID:SU003406
Subject Type:Cultured cells
Subject Species:Homo sapiens
Taxonomy ID:9606
Gender:Not applicable

Factors:

Subject type: Cultured cells; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Sample source Cell line Culture Type Immune checkpoint inhibitor
SA356220CD_A549_3_1_IPI3_rep3Non-small cell lung cancer cells A549 Direct Co-culture Ipilimumab
SA356221CD_A549_3_1_IPI3_rep1Non-small cell lung cancer cells A549 Direct Co-culture Ipilimumab
SA356222CD_A549_3_1_IPI3_rep2Non-small cell lung cancer cells A549 Direct Co-culture Ipilimumab
SA356223CD_A549_3_1_NIV3_rep3Non-small cell lung cancer cells A549 Direct Co-culture Nivolumab
SA356224CD_A549_TW_NIV2_rep2Non-small cell lung cancer cells A549 Direct Co-culture Nivolumab
SA356225CD_A549_3_1_NIV3_rep1Non-small cell lung cancer cells A549 Direct Co-culture Nivolumab
SA356226CD_A549_3_1_CTL3_rep3Non-small cell lung cancer cells A549 Direct Co-culture No treatment
SA356227CD_A549_TW_CTL2_rep2Non-small cell lung cancer cells A549 Direct Co-culture No treatment
SA356228CD_A549_3_1_CTL3_rep1Non-small cell lung cancer cells A549 Direct Co-culture No treatment
SA356229CD_A549_TW_IPI3_rep1Non-small cell lung cancer cells A549 Indirect Co-culture Ipilimumab
SA356230CD_A549_TW_IPI3_rep2Non-small cell lung cancer cells A549 Indirect Co-culture Ipilimumab
SA356231CD_A549_TW_IPI3_rep3Non-small cell lung cancer cells A549 Indirect Co-culture Ipilimumab
SA356232CD_A549_NIV2_rep2Non-small cell lung cancer cells A549 Indirect Co-culture Nivolumab
SA356233CD_A549_TW_NIV3_rep3Non-small cell lung cancer cells A549 Indirect Co-culture Nivolumab
SA356234CD_A549_TW_NIV3_rep1Non-small cell lung cancer cells A549 Indirect Co-culture Nivolumab
SA356235CD_A549_TW_CTL3_rep3Non-small cell lung cancer cells A549 Indirect Co-culture No treatment
SA356236CD_A549_CTL2_rep2Non-small cell lung cancer cells A549 Indirect Co-culture No treatment
SA356237CD_A549_TW_CTL3_rep1Non-small cell lung cancer cells A549 Indirect Co-culture No treatment
SA356238CD_A549_IPI3_rep3Non-small cell lung cancer cells A549 Monoculture Ipilimumab
SA356239CD_A549_IPI3_rep2Non-small cell lung cancer cells A549 Monoculture Ipilimumab
SA356240CD_A549_IPI3_rep1Non-small cell lung cancer cells A549 Monoculture Ipilimumab
SA356241CD_A549_NIV3_rep3Non-small cell lung cancer cells A549 Monoculture Nivolumab
SA356242CD_A549_NIV3_rep1Non-small cell lung cancer cells A549 Monoculture Nivolumab
SA356243CD_A549_3_1_NIV2_rep2Non-small cell lung cancer cells A549 Monoculture Nivolumab
SA356244CD_A549_3_1_CTL2_rep2Non-small cell lung cancer cells A549 Monoculture No treatment
SA356245CD_A549_CTL3_rep1Non-small cell lung cancer cells A549 Monoculture No treatment
SA356246CD_A549_CTL3_rep3Non-small cell lung cancer cells A549 Monoculture No treatment
SA356247CD_H292_TW_IPI1_rep2Non-small cell lung cancer cells H292 Direct Co-culture Ipilimumab
SA356248CD_H292_TW_IPI1_rep3Non-small cell lung cancer cells H292 Direct Co-culture Ipilimumab
SA356249CD_H292_TW_IPI1_rep1Non-small cell lung cancer cells H292 Direct Co-culture Ipilimumab
SA356250CD_H292_TW_NIV1_rep3Non-small cell lung cancer cells H292 Direct Co-culture Nivolumab
SA356251CD_H292_TW_NIV1_rep2Non-small cell lung cancer cells H292 Direct Co-culture Nivolumab
SA356252CD_H292_TW_NIV1_rep1Non-small cell lung cancer cells H292 Direct Co-culture Nivolumab
SA356253CD_H292_TW_CTL1_rep3Non-small cell lung cancer cells H292 Direct Co-culture No treatment
SA356254CD_H292_TW_CTL1_rep2Non-small cell lung cancer cells H292 Direct Co-culture No treatment
SA356255CD_H292_TW_CTL1_rep1Non-small cell lung cancer cells H292 Direct Co-culture No treatment
SA356256CD_H292_IPI1_rep3Non-small cell lung cancer cells H292 Indirect Co-culture Ipilimumab
SA356257CD_H292_IPI1_rep2Non-small cell lung cancer cells H292 Indirect Co-culture Ipilimumab
SA356258CD_H292_IPI1_rep1Non-small cell lung cancer cells H292 Indirect Co-culture Ipilimumab
SA356259CD_H292_NIV1_rep3Non-small cell lung cancer cells H292 Indirect Co-culture Nivolumab
SA356260CD_H292_NIV1_rep1Non-small cell lung cancer cells H292 Indirect Co-culture Nivolumab
SA356261CD_H292_NIV1_rep2Non-small cell lung cancer cells H292 Indirect Co-culture Nivolumab
SA356262CD_H292_CTL1_rep3Non-small cell lung cancer cells H292 Indirect Co-culture No treatment
SA356263CD_H292_CTL1_rep2Non-small cell lung cancer cells H292 Indirect Co-culture No treatment
SA356264CD_H292_CTL1_rep1Non-small cell lung cancer cells H292 Indirect Co-culture No treatment
SA356265CD_H292_3_1_IPI1_rep3Non-small cell lung cancer cells H292 Monoculture Ipilimumab
SA356266CD_H292_3_1_IPI1_rep2Non-small cell lung cancer cells H292 Monoculture Ipilimumab
SA356267CD_H292_3_1_IPI1_rep1Non-small cell lung cancer cells H292 Monoculture Ipilimumab
SA356268CD_H292_3_1_NIV1_rep3Non-small cell lung cancer cells H292 Monoculture Nivolumab
SA356269CD_H292_3_1_NIV1_rep2Non-small cell lung cancer cells H292 Monoculture Nivolumab
SA356270CD_H292_3_1_NIV1_rep1Non-small cell lung cancer cells H292 Monoculture Nivolumab
SA356271CD_H292_3_1_CTL1_rep2Non-small cell lung cancer cells H292 Monoculture No treatment
SA356272CD_H292_3_1_CTL1_rep1Non-small cell lung cancer cells H292 Monoculture No treatment
SA356273CD_H292_3_1_CTL1_rep3Non-small cell lung cancer cells H292 Monoculture No treatment
SA356274CD_PC9_3_1_IPI1_rep3Non-small cell lung cancer cells PC-9 Direct Co-culture Ipilimumab
SA356275CD_PC9_3_1_IPI1_rep2Non-small cell lung cancer cells PC-9 Direct Co-culture Ipilimumab
SA356276CD_PC9_3_1_IPI1_rep1Non-small cell lung cancer cells PC-9 Direct Co-culture Ipilimumab
SA356277CD_PC9_NIV1_rep3Non-small cell lung cancer cells PC-9 Direct Co-culture Nivolumab
SA356278CD_PC9_NIV1_rep2Non-small cell lung cancer cells PC-9 Direct Co-culture Nivolumab
SA356279CD_PC9_NIV1_rep1Non-small cell lung cancer cells PC-9 Direct Co-culture Nivolumab
SA356280CD_PC9_CTL1_rep3Non-small cell lung cancer cells PC-9 Direct Co-culture No treatment
SA356281CD_PC9_CTL1_rep2Non-small cell lung cancer cells PC-9 Direct Co-culture No treatment
SA356282CD_PC9_CTL1_rep1Non-small cell lung cancer cells PC-9 Direct Co-culture No treatment
SA356283CD_PC9_TW_IPI1_rep1Non-small cell lung cancer cells PC-9 Indirect Co-culture Ipilimumab
SA356284CD_PC9_TW_IPI1_rep3Non-small cell lung cancer cells PC-9 Indirect Co-culture Ipilimumab
SA356285CD_PC9_TW_IPI1_rep2Non-small cell lung cancer cells PC-9 Indirect Co-culture Ipilimumab
SA356286CD_PC9_TW_NIV1_rep3Non-small cell lung cancer cells PC-9 Indirect Co-culture Nivolumab
SA356287CD_PC9_TW_NIV1_rep2Non-small cell lung cancer cells PC-9 Indirect Co-culture Nivolumab
SA356288CD_PC9_TW_NIV1_rep1Non-small cell lung cancer cells PC-9 Indirect Co-culture Nivolumab
SA356289CD_PC9_TW_CTL3_rep3Non-small cell lung cancer cells PC-9 Indirect Co-culture No treatment
SA356290CD_PC9_TW_CTL3_repNon-small cell lung cancer cells PC-9 Indirect Co-culture No treatment
SA356291CD_PC9_TW_CTL1_rep1Non-small cell lung cancer cells PC-9 Indirect Co-culture No treatment
SA356292CD_PC9_IPI3_rep3Non-small cell lung cancer cells PC-9 Monoculture Ipilimumab
SA356293CD_PC9_IPI3_rep2Non-small cell lung cancer cells PC-9 Monoculture Ipilimumab
SA356294CD_PC9_IPI3_rep1Non-small cell lung cancer cells PC-9 Monoculture Ipilimumab
SA356295CD_PC9_3_1_NIV1_rep3Non-small cell lung cancer cells PC-9 Monoculture Nivolumab
SA356296CD_PC9_3_1_NIV1_rep2Non-small cell lung cancer cells PC-9 Monoculture Nivolumab
SA356297CD_PC9_3_1_NIV1_rep1Non-small cell lung cancer cells PC-9 Monoculture Nivolumab
SA356298CD_PC9_3_1_CTL1_rep2Non-small cell lung cancer cells PC-9 Monoculture No treatment
SA356299CD_PC9_3_1_CTL1_rep3Non-small cell lung cancer cells PC-9 Monoculture No treatment
SA356300CD_PC9_3_1_CTL1_rep1Non-small cell lung cancer cells PC-9 Monoculture No treatment
Showing results 1 to 81 of 81

Collection:

Collection ID:CO003399
Collection Summary:Using Nivolumab (anti-PD1) and Ipilimumab (anti-CTLA4), we pharmacologically modulated non-small cell lung cancer (NSCLC) cell lines in co-culture with CD8+ T lymphocytes (T CD8+) obtained from healthy blood donors. Two different modalities of co-cultures were established: direct and indirect (with T CD8+ separated from the cancer cells by a Boyden chamber with 1.0 μm pores). 1H-NMR spectroscopy was conducted to characterize the impact of the ICI in the metabolic profile of the immune and cancer cells, as well as the influence of immune cells in the cancer cells exometabolome. Therefore, the media obtained from the established cultures were centrifuged at 135 × g for 5 minutes and the supernatants were collected, stored at -80⁰C and later explored and defined by NMR.
Sample Type:Non-small cell lung cancer

Treatment:

Treatment ID:TR003415
Treatment Summary:For the experimental conditions, cells were exposed to Nivolumab (10 mg/mL, OPDIVO), anti-PD1) or Ipilimumab (5 mg/mL, YERVOY, anti-CTLA-4) for 48 h. The Nivolumab and Ipilimumab concentrations were chosen in accordance to the posology indications from the European Medicines Agency (EMA) and using as reference a male adult with 80 kg and 5 L of blood. The conditions were tested in monoculture or in co-culture with TCD8+.

Sample Preparation:

Sampleprep ID:SP003413
Sampleprep Summary:The supernatant samples were diluted in Milli-Q water to make up 540 μL (150 μL of water was added to 390 μL of supernatant). A volume of 30 µL of phosphate buffer was added to the samples along with 30 μL of a solution of 2.2 mM 3-(trimethylsilyl) propionic 2,2,3,3-d4 acid (TSP) in D2O. TSP was used as an internal reference for quantification and chemical shift.

Analysis:

Analysis ID:AN005383
Analysis Type:NMR
Num Factors:27
Num Metabolites:28
Units:nanomoles

NMR:

NMR ID:NM000285
Analysis ID:AN005383
Instrument Name:Bruker Ultrashield 500 Plus
Instrument Type:FT-NMR
NMR Experiment Type:1D-1H
NMR Comments:Spectra were acquired in a magnetic field of 500 MHz in an Ultrashied 500 Plus spectrometer (Bruker) with a TCI-Z probe at Instituto de Tecnologia Química e Biológica da Universidade NOVA de Lisboa (ITQB-UNL), Oeiras. The spectra analysis was made in TopSpin 4.1 software, according to Chenomx NMR suite 8.11 and Human Metabolome Database (HMDB).
Spectrometer Frequency:500 MHz
NMR Probe:5 mm prodigy TCI-z
NMR Solvent:10% D2O/90% H20
NMR Tube Size:5 mm
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