Dataset Information

Immune monitoring using the predictive power of immune profiles.

ABSTRACT:

Background

We have developed a novel approach to categorize immunity in patients that uses a combination of whole blood flow cytometry and hierarchical clustering.

Methods

Our approach was based on determining the number (cells/?l) of the major leukocyte subsets in unfractionated, whole blood using quantitative flow cytometry. These measurements were performed in 40 healthy volunteers and 120 patients with glioblastoma, renal cell carcinoma, non-Hodgkin lymphoma, ovarian cancer or acute lung injury. After normalization, we used unsupervised hierarchical clustering to sort individuals by similarity into discreet groups we call immune profiles.

Results

Five immune profiles were identified. Four of the diseases tested had patients distributed across at least four of the profiles. Cancer patients found in immune profiles dominated by healthy volunteers showed improved survival (p?ConclusionsComprehensive multi-factorial immune analysis resulting in immune profiles were prognostic, uncovered relationships among immune markers and identified a potential biomarker for the prognosis of cancer. Immune profiles may be useful to streamline evaluation of immune modulating therapies and continue to identify immune based biomarkers.

SUBMITTER: Gustafson MP

PROVIDER: S-EPMC4266565 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Immune monitoring using the predictive power of immune profiles.

Gustafson Michael P MP Lin Yi Y LaPlant Betsy B Liwski Courtney J CJ Maas Mary L ML League Stacy C SC Bauer Philippe R PR Abraham Roshini S RS Tollefson Matthew K MK Kwon Eugene D ED Gastineau Dennis A DA Dietz Allan B AB

Journal for immunotherapy of cancer 20130627

<h4>Background</h4>We have developed a novel approach to categorize immunity in patients that uses a combination of whole blood flow cytometry and hierarchical clustering.<h4>Methods</h4>Our approach was based on determining the number (cells/μl) of the major leukocyte subsets in unfractionated, whole blood using quantitative flow cytometry. These measurements were performed in 40 healthy volunteers and 120 patients with glioblastoma, renal cell carcinoma, non-Hodgkin lymphoma, ovarian cancer or ...[more]

PMID: 25512872

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Project description:The innate immune response (IIR) is a coordinated intracellular signaling network activated by the presence of pathogen-associated molecular patterns that limits pathogen spread and induces adaptive immunity. Although the precise temporal activation of the various arms of the IIR is a critical factor in the outcome of a disease, currently there are no quantitative multiplex methods for its measurement. In this study, we investigate the temporal activation pattern of the IIR in response to intracellular double-stranded RNA stimulation using a quantitative 10-plex stable isotope dilution-selected reaction monitoring-MS assay. We were able to observe rapid activation of both NF-?B and IRF3 signaling arms, with IRF3 demonstrating a transient response, whereas NF-?B underwent a delayed secondary amplification phase. Our measurements of the NF-?B-I?B? negative feedback loop indicate that about 20% of I?B? in the unstimulated cell is located within the nucleus and represents a population that is rapidly degraded in response to double-stranded RNA. Later in the time course of stimulation, the nuclear I?B? pool is repopulated first prior to its cytoplasmic accumulation. Examination of the IRF3 pathway components shows that double-stranded RNA induces initial consumption of the RIG-I PRR and the IRF3 kinase (TBK1). Stable isotope dilution-selected reaction monitoring-MS measurements after siRNA-mediated IRF3 or RelA knockdown suggests that a low nuclear threshold of NF-?B is required for inducing target gene expression, and that there is cross-inhibition of the NF-?B and IRF3 signaling arms. Finally, we were able to measure delayed noncanonical NF-?B activation by quantifying the abundance of the processed (52 kDa) NF-?B2 subunit in the nucleus. We conclude that quantitative proteomics measurement of the individual signaling arms of the IIR in response to system perturbations is significantly enabled by stable isotope dilution-selected reaction monitoring-MS-based quantification, and that this technique will reveal novel insights into the dynamics and connectivity of the IIR.

Dataset Information

Immune monitoring using the predictive power of immune profiles.

Background

Methods

Results

Publications

Immune monitoring using the predictive power of immune profiles.

Similar Datasets

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