Dataset Information

OMIP-068: High-Dimensional Characterization of Global and Antigen-Specific B Cells in Chronic Infection.

ABSTRACT: This 24-color flow cytometry panel focuses on characterizing antigen-specific B cells and precise delineation of B-cell subsets in chronic infections and is applicable to other chronic diseases such as autoimmunity. The panel was optimized for human cryopreserved peripheral blood mononuclear cells (PBMCs). Markers were chosen to extensively distinguish B-cell lineages (CD19, CD20, CD10, CD38, CD24, IgM, IgD, CD27, CD21, CD43, CD5). Inclusion of antigen-specific probes was of high priority in order to assess hepatitis B virus (HBV) antigen-specific B cells for our purposes. These probes can be readily exchanged for other pathogen-specific probes or additional markers for the panel to be tailored to desired research questions beyond HBV. In addition, we included a comprehensive and unique set of functional markers such as chemokine receptors (CXCR3, CXCR5), co-stimulatory molecule (CD86), Fc receptor (CD32), regulatory molecules (BTLA, CD39), and inhibitory markers associated with chronic infections (PD-1, FcRL5, CD11c, CD22) to enable in-depth analysis of global and antigen-specific B cells during chronic infection. © 2020 International Society for Advancement of Cytometry.

SUBMITTER: Cascino K

PROVIDER: S-EPMC7581549 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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OMIP-068: High-Dimensional Characterization of Global and Antigen-Specific B Cells in Chronic Infection.

Cascino Katherine K Roederer Mario M Liechti Thomas T

Cytometry. Part A : the journal of the International Society for Analytical Cytology 20200828 10

This 24-color flow cytometry panel focuses on characterizing antigen-specific B cells and precise delineation of B-cell subsets in chronic infections and is applicable to other chronic diseases such as autoimmunity. The panel was optimized for human cryopreserved peripheral blood mononuclear cells (PBMCs). Markers were chosen to extensively distinguish B-cell lineages (CD19, CD20, CD10, CD38, CD24, IgM, IgD, CD27, CD21, CD43, CD5). Inclusion of antigen-specific probes was of high priority in ord ...[more]

PMID: 32741082

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Project description:BackgroundThe consequences of low prostate-specific antigen (PSA) in high-grade (Gleason 8-10) prostate cancer are unknown.ObjectiveTo evaluate the clinical implications and genomic features of low-PSA, high-grade disease.Design, setting, and participantsThis was a retrospective study of clinical data for 494 793 patients from the National Cancer Data Base and 136 113 patients from the Surveillance, Epidemiology, and End Results program with cT1-4N0M0 prostate cancer (median follow-up 48.9 and 25.0 mo, respectively), and genomic data for 4960 patients from the Decipher Genomic Resource Information Database. Data were collected for 2004-2017.Outcome measurements and statistical analysisMultivariable Fine-Gray and Cox regressions were used to analyze prostate cancer-specific mortality (PCSM) and all-cause mortality, respectively.Results and limitationsFor Gleason 8-10 disease, using PSA 4.1-10.0ng/ml (n=38 719) as referent, the distribution of PCSM by PSA was U-shaped, with an adjusted hazard ratio (AHR) of 2.70 for PSA ≤2.5ng/ml (n=3862, p<0.001) versus 1.97, 1.36, and 2.56 for PSA of 2.6-4.0 (n=4199), 10.1-20.0 (n=17 372), and >20.0ng/ml (n=16 114), respectively. By contrast, the distribution of PCSM by PSA was linear for Gleason ≤7 (using PSA 4.1-10.0ng/ml as the referent, n=359 898), with an AHR of 0.41 (p=0.13) for PSA ≤2.5ng/ml (n=37 812) versus 1.38, 2.28, and 4.61 for PSA of 2.6-4.0 (n=54 152), 10.1-20.0 (n=63 319), and >20.0ng/ml (n=35 459), respectively (pinteraction<0.001). Gleason 8-10, PSA ≤2.5ng/ml disease had a significantly higher PCSM than standard high-risk/very high-risk disease with PSA >2.5ng/ml (AHR 2.15, p=0.002; 47-mo PCSM 14% vs 4.9%). Among Gleason 8-10 patients treated with radiotherapy, androgen deprivation therapy was associated with a survival benefit for PSA >2.5ng/ml (AHR 0.87; p<0.001) but not ≤2.5ng/ml (AHR 1.36; p=0.084; pinteraction=0.021). For Gleason 8-10 tumors, PSA ≤2.5ng/ml was associated with higher expression of neuroendocrine/small-cell markers compared to >2.5ng/ml (p=0.046), with no such relationship for Gleason ≤7 disease.ConclusionsLow-PSA, high-grade prostate cancer has very high risk for PCSM, potentially responds poorly to androgen deprivation therapy, and is associated with neuroendocrine genomic features.Patient summaryIn this study, we found that low-prostate-specific antigen, high-grade prostate cancer has a very high risk for prostate cancer death, may not respond well to androgen deprivation therapy, and is associated with neuroendocrine genomic features. These findings suggest that current nomograms and treatment paradigms may need modification.

Dataset Information

OMIP-068: High-Dimensional Characterization of Global and Antigen-Specific B Cells in Chronic Infection.

Publications

OMIP-068: High-Dimensional Characterization of Global and Antigen-Specific B Cells in Chronic Infection.

Similar Datasets

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