Summary of Study ST002487
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 PR001607. The data can be accessed directly via it's Project DOI: 10.21228/M8013C This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
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.
| Study ID | ST002487 |
| Study Title | Simultaneous targeting of PD-1 and IL2Rβγ with radiation therapy to inhibit pancreatic cancer growth and metastasis - mouse spleen and lymph node T-cell metabolomics |
| Study Summary | Mice were orthotopically implanted with PK5L1940 cells then radiation therapy (8 Gy) administered 7 days post-implantation. PD1-IL2v and aCD25 dosed once per week beginning day 7 post-implantation. Spleen and associated lymph nodes were collected at time of sacrifice and sorted for CD8+ T-cells. The obtained T-cells were profiled by mass spectrometry-based metabolomics. |
| Institute | University of Colorado Denver |
| Last Name | Haines |
| First Name | Julie |
| Address | 12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA |
| julie.haines@cuanschutz.edu | |
| Phone | 3037243339 |
| Submit Date | 2023-02-21 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-03-10 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR001607 |
| Project DOI: | doi: 10.21228/M8013C |
| Project Title: | Simultaneous targeting of PD-1 and IL2Rβγ with radiation therapy to inhibit pancreatic cancer growth and metastasis |
| Project Summary: | In pancreatic ductal adenocarcinoma (PDAC) patients, we show that response to radiation therapy (RT) is characterized by increased IL2Rβ and IL2Rγ and decreased ILR2α expression. The bispecific aPD1-IL2v is a PD-1-targeted IL-2 variant (IL2v) immunocytokine with engineered IL-2 cis-targeted to PD-1 and abolished IL2Rα binding, which enhances tumor-antigen specific T cell activation while reducing regulatory T cell (Treg) suppression. Using aPD1-IL2v in orthotopic PDAC KPC-driven tumor models, we show marked improvement in local and metastatic survival along with profound increase in tumor-infiltrating polyfunctional CD8+ T cell subsets with a transcriptionally and metabolically active phenotype, and preferential activation of antigen-specific CD8+ T cells. In combination with single dose RT, aPD1-IL2v treatment results in a robust, durable expansion of polyfunctional CD8+ T cells, T cell stemness, tumor-specific memory immune response, natural killer (NK) cell activation, and decreased Tregs. These data show that aPD1-IL2v leads to profound local and distant response in PDAC. |
| Institute: | University of Colorado Denver |
| Laboratory: | Lab of Angelo D'Alessandro in collaboration with lab of Sana Karam |
| Last Name: | Haines |
| First Name: | Julie |
| Address: | 12801 E 17th Ave, Room 1303, Aurora, Colorado, 80045, USA |
| Email: | julie.haines@cuanschutz.edu |
| Phone: | 3037243339 |
Subject:
| Subject ID: | SU002577 |
| Subject Type: | Mammal |
| Subject Species: | Mus musculus |
| Species Group: | Mammals |
Factors:
Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)
| mb_sample_id | local_sample_id | factor |
|---|---|---|
| SA248793 | MSL-15 | aCD25 |
| SA248794 | MSL-13 | aCD25 |
| SA248795 | MSL-14 | aCD25 |
| SA248781 | MSL-9 | IL2v |
| SA248782 | MSL-7 | IL2v |
| SA248783 | MSL-8 | IL2v |
| SA248784 | MSL-5 | RT |
| SA248785 | MSL-4 | RT |
| SA248786 | MSL-6 | RT |
| SA248787 | MSL-11 | RT+IL2v |
| SA248788 | MSL-12 | RT+IL2v |
| SA248789 | MSL-10 | RT+IL2v |
| SA248790 | MSL-2 | Untrx |
| SA248791 | MSL-3 | Untrx |
| SA248792 | MSL-1 | Untrx |
| Showing results 1 to 15 of 15 |
Collection:
| Collection ID: | CO002570 |
| Collection Summary: | Spleens of C57BL/6 mice were homogenized to a single cell suspension by mashing the spleen through a 70 uM cell strainer, and the erythrocytes were lysed with ACK (ammonium-chloride-potassium) lysis buffer for 3 min at RT. CD8 T cells were sorted with a CD8-negative selection Stemcell isolation kit following manufacturer instructions. Cells were washed with PBS at 1200RPM, 4degC for 10 minutes and pellets were flash frozen. |
| Sample Type: | Spleen; T-cells |
Treatment:
| Treatment ID: | TR002589 |
| Treatment Summary: | Mice were orthotopically implanted with PK5L1940 cells. RT administered 7 days post-implantation. PD1-IL2v and aCD25 dosed once per week beginning day 7 post-implantation. |
Sample Preparation:
| Sampleprep ID: | SP002583 |
| Sampleprep Summary: | Metabolites from frozen T-cell pellets were extracted with cold 5:3:2 MeOH:acetonitrile:water at a concentration of 4 million cells/mL. Samples were vortexed 30 min at 4 degrees C then supernatants clarified by centrifugation (10 min, 10,000 g, 4 degrees C) and transferred to autosampler vials. |
| Processing Storage Conditions: | 4℃ |
| Extract Storage: | -80℃ |
Chromatography:
| Chromatography ID: | CH003006 |
| Chromatography Summary: | Negative C18 |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Phenomenex Kinetex C18 2.1 x 150 mm, 1.7 um |
| Column Temperature: | 45 |
| Flow Gradient: | 0-0.5 min 0% B, 0.5-1.1 min 0-100% B, 1.1-2.75 min hold at 100% B, 2.75-3 min 100-0% B, 3-5 min hold at 0% B |
| Flow Rate: | 450 uL/min |
| Sample Injection: | 10 uL |
| Solvent A: | 95% water 5% acetonitrile 1 mM ammonium acetate |
| Solvent B: | 95% acetonitrile 5% water 1 mM ammonium acetate |
| Chromatography Type: | Reversed phase |
| Chromatography ID: | CH003007 |
| Chromatography Summary: | Positive C18 |
| Instrument Name: | Thermo Vanquish |
| Column Name: | Phenomenex Kinetex C18 2.1 x 150 mm, 1.7 um |
| Column Temperature: | 45 |
| Flow Gradient: | 0-0.5 min 5% B, 0.5-1.1 min 5-95% B, 1.1-2.75 min hold at 95% B, 2.75-3 min 95-5% B, 3-5 min hold at 5% B |
| Flow Rate: | 450 uL/min |
| Sample Injection: | 10 uL |
| Solvent A: | 100% water 0.1% formic acid |
| Solvent B: | 100% acetonitrile 0.1% formic acid |
| Chromatography Type: | Reversed phase |
Analysis:
| Analysis ID: | AN004060 |
| Analysis Type: | MS |
| Chromatography ID: | CH003006 |
| Num Factors: | 5 |
| Num Metabolites: | 50 |
| Units: | peak area |
| Analysis ID: | AN004061 |
| Analysis Type: | MS |
| Chromatography ID: | CH003007 |
| Num Factors: | 5 |
| Num Metabolites: | 69 |
| Units: | peak area |
