Peripheral Blood CD8+ T-Lymphocyte Immune Response in Benign and Subpopulations of Breast Cancer Patients
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ABSTRACT:
SUBMITTER: Lenart M
PROVIDER: S-EPMC11204132 | biostudies-literature | 2024 Jun
REPOSITORIES: biostudies-literature
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Project description:Peripheral blood CD8+ T-lymphocytes play a crucial role in cell-mediated immunity and tumour-related immune responses in breast cancer. The protein profile analysis of CD8+ T-lymphocytes in benign, Luminal A, Luminal B and triple-negative breast cancer (TNBC) patients in comparison to healthy control via a label-free proteomic quantification and gene set enrichment analysis (GSEA) were performed. The results confirmed that the most significantly of RNA degradation signalling pathway was down-regulated in all groups (benign, Luminal A, Luminal B, TNBC) was observed. Given the immunological role that T cells play in the treatment of disease, a better knowledge of RNA metabolism, i.e., the role that mRNA degradation pathways play in human physiology and pathology may lead to novel approaches to the therapeutic use of T cells.
2024-07-09 | PXD051985 | Pride
Project description:Background Obesity, a public health problem, is a state of metainflammation that influences the development of chronic degenerative diseases, particularly in patients with severe obesity. Objective The objective of this study was to evidence immunometabolic differences in patients with different degrees of obesity, including severe obesity, by determining correlations between lymphocyte subpopulations and metabolic, body composition, and clinical variables. Methods Peripheral blood immune cells (CD4+, CD8+ memory and effector T lymphocytes) were analyzed, and measures of body composition, blood pressure, and biochemical composition (glucose, glycated hemoglobin (HbA1c), insulin, C-reactive protein (CRP), and the lipid profile) were carried out in patients with different degrees of obesity. Results The patients were classified according to total body fat (TBF) percentage as normal body fat, class 1 and 2 obesity, class 3 obesity, and class 4 obesity. The greater the TBF percentage, the more pronounced the differences in body composition (such as a decrease in the fat-free mass (FFM) that is defined as sarcopenic obesity) and the immunometabolic profile. There was an increase of CD3+ T lymphocytes (mainly CD4+, CD4+CD62-, and CD8+CD45RO+ T lymphocytes) and an increase in the TBF percentage (severity of obesity). Conclusions The correlations between lymphocyte subpopulations and metabolic, body composition, and clinical variables demonstrated the existence of a chronic, low-intensity inflammatory process in obesity. Therefore, measuring the immunometabolic profile by means of lymphocyte subpopulations in patients with severe obesity could be useful to determine the severity of the disease and the increased risk of presenting obesity-associated chronic degenerative diseases.
| S-EPMC10274585 | biostudies-literature
Project description:ObjectiveAtherosclerosis is characterized by a chronic inflammatory response involving activated T cells and impairment of natural killer (NK) cells. An increased T cell activity has been associated with plaque instability and risk of acute cardiac events. Lymphocyte analyses in blood are widely used to evaluate the immune status. However, peripheral blood contains only a minor proportion of lymphocytes. In this study, we hypothesized that thoracic lymph nodes from patients with stable angina (SA) and acute coronary syndrome (ACS) might add information to peripheral blood analyses.MethodsPeripheral blood and lymph nodes were collected during coronary by-pass surgery in 13 patients with SA and 13 patients with ACS. Lymphocyte subpopulations were assessed by flow cytometry using antibodies against CD3, CD4, CD8, CD19, CD16/56, CD25, Foxp3, CD69, HLA-DR, IL-18 receptor (R) and CCR4.ResultsLymph nodes revealed a lymphocyte subpopulation profile substantially differing from that in blood including a higher proportion of B cells, lower proportions of CD8(+) T cells and NK cells and a 2-fold higher CD4/CD8 ratio. CD4(+)CD69(+) cells as well as Foxp3(+) regulatory T cells were markedly enriched in lymph nodes (p<0.001) while T helper 1-like (CD4(+)IL-18R+) cells were more frequent in blood (p<0.001). The only significant differences between ACS and SA patients involved NK cells that were reduced in the ACS group. However, despite being reduced, the NK cell fraction in ACS patients contained a significantly higher proportion of IL-18R(+) cells compared with SA patients (p<0.05).ConclusionThere were several differences in lymphocyte subpopulations between blood and lymph nodes. However, the lymphocyte perturbations in peripheral blood of ACS patients compared with SA patients were not mirrored in lymph nodes. The findings indicate that lymph node analyses in multivessel coronary artery disease may not reveal any major changes in the immune response that are not detectable in blood.
| S-EPMC3291561 | biostudies-literature
Project description:DNA damage occurs constantly in every cell triggered by endogenous processes of replication and metabolism, and external influences such as ionizing radiation and intercalating chemicals. Large sets of proteins are involved in sensing, stabilizing and repairing this damage including control of cell cycle and proliferation. Some of these factors are phosphorylated upon activation and can be used as biomarkers of DNA damage response (DDR) by flow and mass cytometry. Differential survival rates of lymphocyte subsets in response to DNA damage are well established, characterizing NK cells as most resistant and B cells as most sensitive to DNA damage. We investigated DDR to low dose gamma radiation (2Gy) in peripheral blood lymphocytes of 26 healthy donors and 3 patients with ataxia telangiectasia (AT) using mass cytometry. γH2AX, p-CHK2, p-ATM and p53 were analyzed as specific DDR biomarkers for functional readouts of DNA repair efficiency in combination with cell cycle and T, B and NK cell populations characterized by 20 surface markers. We identified significant differences in DDR among lymphocyte populations in healthy individuals. Whereas CD56+CD16+ NK cells showed a strong γH2AX response to low dose ionizing radiation, a reduced response rate could be observed in CD19+CD20+ B cells that was associated with reduced survival. Interestingly, γH2AX induction level correlated inversely with ATM-dependent p-CHK2 and p53 responses. Differential DDR could be further noticed in naïve compared to memory T and B cell subsets, characterized by reduced γH2AX, but increased p53 induction in naïve T cells. In contrast, DDR was abrogated in all lymphocyte populations of AT patients. Our results demonstrate differential DDR capacities in lymphocyte subsets that depend on maturation and correlate inversely with DNA damage-related survival. Importantly, DDR analysis of peripheral blood cells for diagnostic purposes should be stratified to lymphocyte subsets.
| S-EPMC8478158 | biostudies-literature
Project description:Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis with a 5-year survival of less than 10%. More knowledge of the immune response developed in patients with PDAC is pivotal to develop better combination immune therapies to improve clinical outcome. In this study, we used mass cytometry time-of-flight to undertake an in-depth characterization of PBMCs from patients with PDAC and examine the differences with healthy controls and patients with benign diseases of the biliary system or pancreas. Peripheral blood mononuclear cells from patients with PDAC or benign disease are characterized by the increase of pro-inflammatory cells, as CD86+ classical monocytes and memory T cells expressing CCR6+ and CXCR3+, associated with T helper 1 (Th1) and Th17 immune responses, respectively. However, PBMCs from patients with PDAC present also an increase of CD39+ regulatory T cells and CCR4+CCR6-CXCR3- memory T cells, suggesting Th2 and regulatory responses. Concluding, our results show PDAC develops a multifaceted immunity, where a proinflammatory component is accompanied by regulatory responses, which could inhibit potential antitumor mechanisms.
| S-EPMC11247553 | biostudies-literature
Project description:BACKGROUND:Peripheral blood transcriptome profiling is a potentially important tool for disease detection. We utilize this technique in a case-control study to identify candidate transcriptomic biomarkers able to differentiate women with breast lesions from normal controls. METHODS:Whole blood samples were collected from 50 women with high-risk breast lesions, 57 with breast cancers and 44 controls (151 samples). Blood gene expression profiling was carried out using microarray hybridization. We identified blood gene expression signatures using AdaBoost, and constructed a predictive model differentiating breast lesions from controls. Model performance was then characterized by AUC sensitivity, specificity and accuracy. Biomarker biological processes and functions were analyzed for clues to the pathogenesis of breast lesions. RESULTS:Ten gene biomarkers were identified (YWHAQ, BCLAF1, WSB1, PBX2, DDIT4, LUC7L3, FKBP1A, APP, HERC2P2, FAM126B). A ten-gene panel predictive model showed discriminatory power in the test set (sensitivity: 100%, specificity: 84.2%, accuracy: 93.5%, AUC: 0.99). These biomarkers were involved in apoptosis, TGF-beta signaling, adaptive immune system regulation, gene transcription and post-transcriptional protein modification. CONCLUSION:A promising method for the detection of breast lesions is reported. This study also sheds light on breast cancer/immune system interactions, providing clues to new targets for breast cancer immune therapy.
| S-EPMC7272048 | biostudies-literature
Project description:The COVID-19 pandemic caused by SARS-CoV-2 has reached 5.5 million deaths worldwide, generating a huge impact globally. This highly contagious viral infection produces a severe acute respiratory syndrome that includes cough, mucus, fever and pneumonia. Likewise, many hospitalized patients develop severe pneumonia associated with acute respiratory distress syndrome (ARDS), along an exacerbated and uncontrolled systemic inflammation that in some cases induces a fatal cytokine storm. Although vaccines clearly have had a beneficial effect, there is still a high percentage of unprotected patients that develop the pathology, due to an ineffective immune response. Therefore, a thorough understanding of the modulatory mechanisms that regulate the response to SARS-CoV-2 is crucial to find effective therapeutic alternatives. Previous studies describe the relevance of Neddylation in the activation of the immune system and its implications in viral infection. In this context, the present study postulates Neddylation, a reversible ubiquitin-like post-translational modification of proteins that control their stability, localization and activity, as a key regulator in the immune response against SARS-CoV-2. For the first time, we describe an increase in global neddylation levels in COVID-19 in the serum of patients, which is particularly associated with the early response to infection. In addition, the results showed that overactivation of neddylation controls activation, proliferation, and response of peripheral blood mononuclear cells (PBMCs) isolated from COVID-19 patients. Inhibition of neddylation, and the subsequent avoidance of activated PBMCs, reduces cytokine production, mainly IL-6 and MCP-1 and induce proteome modulation, being a critical mechanism and a potential approach to immunomodulate COVID-19 patients.
| S-EPMC9277603 | biostudies-literature
Project description:Bovine paratuberculosis is a serious chronic disease of the gastrointestinal tract caused by Mycobacterium avium subspecies paratuberculosis (MAP). The aim of this study was to detect proteomic changes in peripheral blood mononuclear cells (PBMC) from cows of the same herd with different MAP infection status after co-incubation with viable MAP in vitro using label-free LC-MS/MS. Our data contribute to a better understanding of the bovine immune response and mechanisms of susceptibility to MAP.
2023-03-10 | PXD036881 | Pride
Project description:The COVID-19 pandemic caused by SARS-CoV-2 has reached 5.5 million deaths worldwide, causing a huge impact globally. This highly contagious viral infection produces a severe acute respiratory syndrome that includes cough, mucus, fever and pneumonia. Likewise, many hospitalized patients develop severe pneumonia associated with acute respiratory distress syndrome (ARDS), besides an exacerbated and uncontrolled systemic inflammation which in some cases induce lethal cytokine storm. Although vaccines have clearly had a beneficial effect on disease development, there is still a high percentage of patients who develop pathology related to ineffective immune system response. Therefore, a thorough understanding of the modulatory mechanisms that regulate the response to SARS-CoV-2 is crucial to find effective therapeutic alternatives. Previous studies describe the relevance of Neddylation in immune system activation further its implications in viral infection. In this context, the present study postulates Neddylation, a reversible ubiquitin-like post-translational modification of proteins and controls their stability, localization and activity, as a key regulator in the immune response against SARS-CoV-2. For the first time, we describe an increase of serum global neddylation levels of COVID-19 patients particularly associated in the early response of the infection. In addition, the results showed that overactivation of neddylation control activation, proliferation, and response of peripheral blood mononuclear cells (PBMCs) derived from COVID-19 patients. Inhibition of neddylation and subsequent avoidance of activation of PBMCs, which reduces cytokine production and proteome modulation, may therefore be a critical mechanism and an efficient therapeutic approach to immunomodulate COVID -19 patients and avoid the much-feared cytokine storm.
2022-08-02 | PXD033673 | Pride
Project description:BackgroundWith the increasing incidence of breast lesions, the differential diagnosis between benign lesions and breast cancer (BCa) has become a big challenge. Host peripheral blood mononuclear cells (PBMCs) could undergo changes in DNA methylation upon disease progression. However, the clinical value of DNA methylation of PBMCs in differentiating benign lesions and BCa is still unclear.MethodsDNA of PBMCs was isolated and the methylation status of PBMCs in patients with BCa and benign breast nodules was detected by using Illumina Infinium methylation EPIC array. The specific methylation targets were validated by pyrosequencing, Targeted Bisulfite Sequencing Assay, and Multiplex Methylation PCR Assay(MMPA).Resultscg26977936, cg23351954, and cg27209741 were validated as differentially methylated and showed the potential diagnostic values (sensitivity and specificity were 90.0%/53.3%, 43.3%/90.0%, 90.0%/43.3%, respectively). Moreover, a diagnostic model was established using these 3 CGs through logistic regression analysis, and the AUC reached 0.837. Next, this diagnostic model was validated in another, independent cohort with Targeted Bisulfite Sequencing Assay, and the clinical value in distinguishing benign and malignant breast disease was also confirmed (AUC = 0.827, P < 0.05). Finally, to better meet the need for the clinical test, we further validated the differential diagnostic efficacy of the 2 hypermethylated DMPs by establishing a Multiplex Methylation PCR Assay by coupling the 5'-flap endonuclease activity of Taq DNA polymerase and molecular beacon reporters.ConclusionsDNA methylation changes in PBMCs showed great potential in discriminating BCa patients from breast benign lesion patients and may serve as a novel predictor in clinical applications.
| S-EPMC11600940 | biostudies-literature