scholarly journals Prostate Cancer: Early Detection and Assessing Clinical Risk Using Deep Machine Learning of High Dimensional Peripheral Blood Flow Cytometric Phenotyping Data

2021 ◽  
Vol 12 ◽  
Author(s):  
Georgina Cosma ◽  
Stéphanie E. McArdle ◽  
Gemma A. Foulds ◽  
Simon P. Hood ◽  
Stephen Reeder ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Specific Antigen ◽  
Effector Memory ◽  
Memory Cells ◽  
Prostate Disease ◽  
Clinical Risk ◽  
High Risk Disease ◽  
Effector Memory Cells ◽  
Benign Prostate ◽  
Asymptomatic Men

Detecting the presence of prostate cancer (PCa) and distinguishing low- or intermediate-risk disease from high-risk disease early, and without the need for potentially unnecessary invasive biopsies remains a significant clinical challenge. The aim of this study is to determine whether the T and B cell phenotypic features which we have previously identified as being able to distinguish between benign prostate disease and PCa in asymptomatic men having Prostate-Specific Antigen (PSA) levels < 20 ng/ml can also be used to detect the presence and clinical risk of PCa in a larger cohort of patients whose PSA levels ranged between 3 and 2617 ng/ml. The peripheral blood of 130 asymptomatic men having elevated Prostate-Specific Antigen (PSA) levels was immune profiled using multiparametric whole blood flow cytometry. Of these men, 42 were subsequently diagnosed as having benign prostate disease and 88 as having PCa on biopsy-based evidence. We built a bidirectional Long Short-Term Memory Deep Neural Network (biLSTM) model for detecting the presence of PCa in men which combined the previously-identified phenotypic features (CD8+CD45RA-CD27-CD28- (CD8+ Effector Memory cells), CD4+CD45RA-CD27-CD28- (CD4+ Effector Memory cells), CD4+CD45RA+CD27-CD28- (CD4+ Terminally Differentiated Effector Memory Cells re-expressing CD45RA), CD3-CD19+ (B cells), CD3+CD56+CD8+CD4+ (NKT cells) with Age. The performance of the PCa presence ‘detection’ model was: Acc: 86.79 ( ± 0.10), Sensitivity: 82.78% (± 0.15); Specificity: 95.83% (± 0.11) on the test set (test set that was not used during training and validation); AUC: 89.31% (± 0.07), ORP-FPR: 7.50% (± 0.20), ORP-TPR: 84.44% (± 0.14). A second biLSTM ‘risk’ model combined the immunophenotypic features with PSA to predict whether a patient with PCa has high-risk disease (defined by the D’Amico Risk Classification) achieved the following: Acc: 94.90% (± 6.29), Sensitivity: 92% (± 21.39); Specificity: 96.11 (± 0.00); AUC: 94.06% (± 10.69), ORP-FPR: 3.89% (± 0.00), ORP-TPR: 92% (± 21.39). The ORP-FPR for predicting the presence of PCa when combining FC+PSA was lower than that of PSA alone. This study demonstrates that AI approaches based on peripheral blood phenotyping profiles can distinguish between benign prostate disease and PCa and predict clinical risk in asymptomatic men having elevated PSA levels.

Predictive value of circulating B cells and T cell subsets in melanoma patients treated with neoadjuvant ipilimumab and interferon.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15036-e15036
Author(s):  
Arjun Khunger ◽  
Ghanashyam Sarikonda ◽  
Jenn Tsau ◽  
Zeni Alfonso ◽  
Jane Gao ◽  
...  
Keyword(s):  
T Cells ◽  
B Cells ◽  
Peripheral Blood ◽  
Post Treatment ◽  
T Cell Subsets ◽  
Effector Memory ◽  
Memory Cells ◽  
Color Flow ◽  
Time Points ◽  
Effector Memory Cells

e15036 Background: Patients with locally/regionally advanced melanoma were treated on a clinical trial with a neoadjuvant combination of ipilimumab (ipi) and high dose IFNα2b (HDI) (Tarhini et al, JITC 2018). In this study, immune cell composition in peripheral blood samples collected at various time points was measured to determine any correlation with clinical outcomes and investigate the immune modulating effect of the combination therapy. Methods: Patients were randomized to neoadjuvant ipi at 3 mg/kg or 10 mg/kg, both given in combination with HDI. Tumor radiologic responses were designated as complete (CR), partial (PR), stable disease (SD) or disease progression (PD). Pathologic complete response (pCR) was defined as absence of viable tumor on histologic assessment. Peripheral blood mononuclear cells (PBMC) from treated patients (N = 28) were tested at baseline (before initiating ipi-HDI), then at 6-weeks, 3-months and 12-months (following neoadjuvant ipi-HDI). High complexity (14-color) flow cytometry analysis was performed to detect key immunological biomarkers including myeloid derived suppressor cells (MDSCs), B cells, regulatory T cells (Tregs), PD-1 and TIM3 expression on T-cells, and differentiation of T-cells into Th1, Th2 or Th17 phenotype at different time points during systemic immunotherapy. Statistical significance was determined using R-package employing Kruskal’s test. Results: Lower levels of peripheral Tregs (p = 0.02), MDSCs (p = 0.05), and CD4 effector memory cells (p = 0.04) at 3-months post treatment correlated with radiologic response. In addition, lower change from baseline at 3 months in CD4/CD8 ratio (p = 0.04), levels of Tregs (p = 0.01) and CD4 effector memory cells (p = 0.02) was associated with radiologic response. Patients exhibiting pCR had significantly lower Tregs (p = 0.04) at 6-months post treatment and significantly higher CD8 central memory cells at both 3 months (p = 0.04) and 12 month time-points (p = 0.01) as compared to patients without pCR. Finally, patients without pCR had significantly lower change from baseline in CD19 B cells at 6 months (p = 0.01) and 12 months (p = 0.04) as compared to patients with pCR. Conclusions: Our data demonstrates that the levels of immunosuppressive cells including Tregs and MDSCs in periphery are negatively associated with response. Higher levels of CD8 memory cells and B cells on-treatment are associated with clinical benefit.

scholarly journals CHARACTERIZATION OF CENTRAL AND EFFECTOR CD4⁺ MEMORY CELLS IN PSORIASIS

2021 ◽  
Vol 23 (4) ◽  
pp. 969-974
Author(s):  
A. V. Kolerova ◽  
D. A. Mikailova ◽  
M. A. Beimanova ◽  
E. A. Blinova
Keyword(s):  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Central Memory ◽  
Effector Memory ◽  
Memory Cells ◽  
Peripheral Blood Mononuclear ◽  
Healthy Donors ◽  
Central Memory Cells ◽  
Effector Memory Cells ◽  
Severity Of The Disease

Psoriasis is a chronic autoimmune disease in which the skin and joints are involved in the pathological process. It was found that the recurrence of rashes in this disease occurs due to the resident memory cells of the skin. The number of CD4+CCR3+ effector memory cells in peripheral blood correlates with the severity of the disease. Therefore, the aim of our work is to study the phenotype of peripheral blood memory cells in patients with psoriasis.The study included 6 healthy donors: average age – 45.4 (min – 29, max – 55), women – 3, men – 3; 10 patients with psoriasis: women – 4, men – 6, average age – 37.3 (min – 23, max – 57), of which 5 patients with PASI > 10 and 5 patients with PASI < 10. The exclusion criteria for the study were the presence of autoimmune, oncological and hematological diseases, systemic therapy with immunosuppressive drugs for 1 month. Patients signed informed consent to participate in the study. Isolation of peripheral blood mononuclear cells was performed in a density gradient of ficoll-urographin (p = 1.082 g/L). Then cells were stained with fluorochrome-conjugated monoclonal antibodies to surface markers of central (Tcm) and effector (Tem) CD4+ memory cells (CD4, CD45RO, CD197), the α-chain of the IL-7 receptor (CD127), and the γ-chain of the IL-7 receptor (CD132). Statistical analysis of the data obtained was performed using the Statistica 6.0 software package.The percent of Tcm in the peripheral blood of donors was 33.4% (in – 18.2, max – 43.7), Tem – 28.7% (min – 13.6, max – 38.9), in patients with psoriasis: Tcm – 28.65% (min – 13.3, max – 59.6), Tem – 21.5% (min – 9.3, max – 38.6). In the peripheral blood of patients with psoriasis, among the central CD4+ memory cells, the proportion of CD127+CD132- -cells is 26.00%, CD127+CD132+ – 1.69%, CD127+CD132- – 69.00%, CD127- CD132+ – 1.94%. Among effector CD4+ memory cells, the proportion of CD127+CD132- -cells is 23.58%, CD127+CD132+ – 1.18%, CD127+CD132- – 69.84%, CD127- CD132+ – 0.70%. A direct correlation was found between the number of CD127- CD132+ central memory cells and the PASI value (r = 0.639, p < 0.05).In patients with psoriasis, the proportion of central memory cells is higher than in healthy donors, while the number of effector memory cells is lower. A direct correlation was found between the number of central cells expressing the γ-chain of the IL-7 receptor and the severity of the disease. Activated memory cells are characterized by high expression of CD132. It can be assumed that this population of memory cells plays a role in maintaining autoimmune inflammation in patients with this disease, and also participates in the repopulation of skin resident memory cells. 

Effect of KGF (Palifermin) On Immune Reconstitution After Autologous Transplantation for Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1152-1152
Author(s):  
Emmanuel Clave ◽  
Corinne Douay ◽  
Claire Rabian ◽  
Maryvonnick Carmagnat ◽  
Helene Moins ◽  
...  
Keyword(s):  
Immune Deficiency ◽  
Multiple Myeloma ◽  
T Cell ◽  
Clinical Application ◽  
Peripheral Blood ◽  
Immune Reconstitution ◽  
Autologous Transplantation ◽  
Effector Memory ◽  
Memory Cells ◽  
Effector Memory Cells

Abstract Abstract 1152 Poster Board I-174 Introduction Human-keratinocyte growth factor 1(KGF) is currently being evaluated in clinical trials for its safety and efficacy in preventing mucosal damage from irradiation and after bone marrow transplantation (BMT). It has been suggested that, besides having preventive effects on oral mucositis, it may also have immunomodulating effects by uniquely protecting thymic epithelial cells. A potential clinical application of KGF is the amelioration of prolonged post BMT-immune deficiency in BMT recipients. In animal models of autologous and allogeneic BMT, KGF administration during BMT resulted in enhanced thymopoiesis and increased peripheral T-cell numbers. Therefore, a potential clinical application of KGF is the improvement of prolonged post BMT-immune deficiency in BMT recipients. Thymopoiesis can be assessed by analysis of T-cell receptor excision circles (TREC). This marker for recent thymic emigrants might be a novel prognostic factor for outcome after transplantation in multiple myeloma patients. We investigated the potential influence of KGF on immune reconstitution after autologous transplantation for myeloma using this marker. Materials and Methods Twenty-four myeloma patients from a single institution were treated homogeneously with the induction combination bortezomib (Velcade®) plus dexamethasone (DXM), followed by high dose melphalan (140-200 mg/m2) and an autologous transplantation with peripheral blood stem cells. Patients were randomized for KGF treatment in 2 groups, 11 having received three doses of palifermin (Kepivance®) (60 μg/kg once daily i.v.) pre- and post-conditioning regimen (total six doses). Blood samples were drawn at diagnosis, before BMT, and at 1, 3, 6, 9, 12 and 18 months post BMT. We analysed signal joint (sj) TREC in peripheral blood lymphocytes using quantitative RT-PCR. The percentage and absolute numbers of lymphocyte populations were monitored by flow cytometry. Values were expressed as means ± SEM. Patient groups were compared by the Mann-Whitney test. Results Both CD4+ and CD8+ naïve T cells (CD45RA+ CCR7+) were strongly decreased by pretransplantation bortezomib plus DXM treatment. SjTREC decreased sharply after transplantation and returned to baseline after 1 year without differences between the two groups of patients. Natural regulatory T lymphocytes (phenotypically assessed as CD4+ CD25 high, CD127 low) were not modified by KGF treatment either. Notably, the CD3+ cell population was significantly higher during the first 3 months post BMT in KGF treated patients (1518 ± 380 vs 821 ± 105 CD3+/blood mL, p = 0.032 at 1 month post BMT). This was related to a higher CD8+ cell counts, specifically in the CD8 effector memory cells (assessed as CD45 RA- CCR7-) (790 ± 320 vs 292 ± 55, p< 0.05 at 1 month post BMT). No correlation was found with documented infectious complications, relapse or survival. Conclusions These data suggest that, unexpectedly, the main effect of KGF on immunity in that autologous BMT setting, is not to be accounted by changes in thymic function but rather by the peripheral expansion of CD8+ effector memory cells which could be favoured by the treatment prior BMT and/or by the post-BMT lymphopenia. Disclosures No relevant conflicts of interest to declare.

Analysis Of Circulating Rhinovirus-Specific CD4+ T Cells Using Novel MHC Class II Tetramers Reveals Marked Expansion Of Effector Memory Cells In Infected Subjects

2014 ◽  
Vol 133 (2) ◽  
pp. AB292
Author(s):  
Lyndsey Muehling ◽  
Rachana Agrawal ◽  
Julia Wisniewski ◽  
Paul Wright ◽  
William W. Kwok ◽  
...  
Keyword(s):  
T Cells ◽  
Mhc Class Ii ◽  
Cd4 T Cells ◽  
Class Ii ◽  
Effector Memory ◽  
Memory Cells ◽  
Effector Memory Cells

scholarly journals Human CCR5high effector memory cells perform CNS parenchymal immune surveillance via GZMK-mediated transendothelial diapedesis

Brain ◽  
2019 ◽  
Vol 142 (11) ◽  
pp. 3411-3427 ◽  
Author(s):  
Sebastian Herich ◽  
Tilman Schneider-Hohendorf ◽  
Astrid Rohlmann ◽  
Maryam Khaleghi Ghadiri ◽  
Andreas Schulte-Mecklenbeck ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Blood Brain Barrier ◽  
Immune Cell ◽  
Immune Surveillance ◽  
Brain Barrier ◽  
Effector Memory ◽  
Cell Populations ◽  
Memory Cells ◽  
Hiv Patients ◽  
Effector Memory Cells

Specific immune-cell populations patrol the CNS in search of pathogens and tumours. Herich et al. identify CD4+ CCR5high GzmK+ effector-memory cells as a brain-surveilling subpopulation capable of crossing the uninflamed blood-brain barrier, and reveal alterations in this population in HIV+ patients with neurological symptoms and in patients with multiple sclerosis.

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