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Cytometry. Part a : the Journal of the... Jan 2024We have developed a 31-color panel to define the steady-state phenotype of T cells in human peripheral blood (Table 1). The panel presented here was optimized using...
We have developed a 31-color panel to define the steady-state phenotype of T cells in human peripheral blood (Table 1). The panel presented here was optimized using cryopreserved peripheral blood mononuclear cells (PBMC). The markers included in this panel were chosen in order to characterize the steady-state phenotype of T cells and includes markers (CD45RA, CD45RO, CCR7, CD95) to distinguish the main subsets (e.g., naïve, T , T , T , T etc.) of CD4, CD8, and γδ T cells. This panel also includes markers for the identification of differentiation status (CD27, CD28), activation/antigen experience status (CD11a, CD49d, CD38, HLA-DR, CD56, and CD39), co-inhibitory marker expression (PD-1, TIM-3), and CD4 T helper subsets (CXCR3, CXCR5, CCR4, CCR6, Foxp3, CD25, and CD127). This optimized panel provides a broad assessment of the steady-state phenotype of human T cells.
Topics: Humans; Leukocytes, Mononuclear; Flow Cytometry; T-Lymphocytes; Leukocyte Common Antigens; Phenotype; T-Lymphocyte Subsets
PubMed: 37814476
DOI: 10.1002/cyto.a.24799 -
Current Neurology and Neuroscience... Dec 2023Given the invasive and high-risk nature of brain surgery, the need for non-invasive biomarkers obtained from the peripheral blood is greatest in tumors of the central... (Review)
Review
PURPOSE OF REVIEW
Given the invasive and high-risk nature of brain surgery, the need for non-invasive biomarkers obtained from the peripheral blood is greatest in tumors of the central nervous system (CNS). In this comprehensive review, we highlight recent advances in blood biomarker development for adult and pediatric brain tumors.
RECENT FINDINGS
We summarize recent blood biomarker development for CNS tumors across multiple key analytes, including peripheral blood mononuclear cells, cell-free DNA, cell-free RNA, proteomics, circulating tumor cells, and tumor-educated platelets. We also discuss methods for enhancing blood biomarker detection through transient opening of the blood-brain barrier. Although blood-based biomarkers are not yet used in routine neuro-oncology practice, this field is advancing rapidly and holds great promise for improved and non-invasive management of patients with brain tumors. Prospective and adequately powered studies are needed to confirm the clinical utility of any blood biomarker prior to widespread clinical implementation.
Topics: Child; Adult; Humans; Biomarkers, Tumor; Leukocytes, Mononuclear; Prospective Studies; Brain Neoplasms; Neoplastic Cells, Circulating
PubMed: 37943477
DOI: 10.1007/s11910-023-01321-y -
Circulation Dec 2023Rivaroxaban plus aspirin compared with aspirin alone reduced major cardiac and ischemic limb events after lower extremity revascularization (LER) in the VOYAGER PAD... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Rivaroxaban plus aspirin compared with aspirin alone reduced major cardiac and ischemic limb events after lower extremity revascularization (LER) in the VOYAGER PAD (Vascular Outcomes Study of ASA Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization for Peripheral Artery Disease) trial. The effect has not been described in patients undergoing endovascular LER.
METHODS
The VOYAGER PAD trial randomized 6564 patients with symptomatic peripheral artery disease to a double-blinded treatment with 2.5 mg of rivaroxaban BID or matching placebo and 100 mg of aspirin daily. The primary efficacy outcome was a composite of acute limb ischemia, major amputation of a vascular pathogenesis, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety end point was Thrombolysis in Myocardial Infarction major bleeding. A prespecified subgroup of patients who underwent endovascular revascularization was included.
RESULTS
Endovascular LER occurred in 4379 (66.7%) patients and surgical LER in 2185 (33.3%). Over a 3-year follow-up, rivaroxaban reduced the risk of the primary outcome by 15% (hazard ratio [HR], 0.85 [95% CI, 0.76-0.96]) with an absolute risk reduction of 0.92% at 6 months and 1.04% at 3 years and a consistent benefit in those receiving endovascular (HR, 0.89 [95% CI, 0.76-1.03]) or surgical LER (HR, 0.81 [95% CI, 0.67-0.98]; interaction=0.43). For endovascular-treated patients, rivaroxaban reduced the risk of acute limb ischemia or major amputation of a vascular pathogenesis by 30% (HR, 0.70 [95% CI, 0.54-0.90]; =0.005) with an absolute risk reduction of 1.0% at 6 months and 2.0% at 3 years compared with aspirin alone. Among endovascular-treated patients, the median duration of concomitant dual antiplatelet therapy with clopidogrel treatment was 31 days (interquartile range, 30-58). There was a consistent benefit for rivaroxaban regardless of background clopidogrel. Thrombolysis in Myocardial Infarction major bleeding was significantly higher for the rivaroxaban and aspirin group for the endovascular cohort (HR, 1.66 [95% CI, 1.06-2.59]) with an absolute risk increase of 0.9% at 3 years with no increase in intracranial or fatal bleeding observed (HR, 0.86 [95% CI, 0.40-1.87]; =0.71). Mortality with rivaroxaban was higher in the endovascular-treated patients (HR, 1.24 [95% CI, 1.02-1.52]), although this finding was isolated to specific regions.
CONCLUSIONS
Rivaroxaban added to aspirin or dual antiplatelet therapy after LER for peripheral artery disease reduces ischemic risk and increases major bleeding without an increased risk of intracranial or fatal bleeding. These benefits are consistent in those treated with endovascular and surgical approaches with significant benefits for major adverse limb events. These data support the use of rivaroxaban in addition to aspirin or dual antiplatelet therapy after endovascular intervention for symptomatic peripheral artery disease.
Topics: Humans; Aspirin; Rivaroxaban; Platelet Aggregation Inhibitors; Clopidogrel; Hemorrhage; Peripheral Arterial Disease; Myocardial Infarction; Ischemia; Drug Therapy, Combination
PubMed: 37850397
DOI: 10.1161/CIRCULATIONAHA.122.063806 -
Clinical Immunology (Orlando, Fla.) Oct 2023Regulatory T cells (Tregs) are key regulators for the inflammatory response and play a role in maintaining the immune tolerance. Type 1 diabetes (T1D) is a relatively... (Review)
Review
Regulatory T cells (Tregs) are key regulators for the inflammatory response and play a role in maintaining the immune tolerance. Type 1 diabetes (T1D) is a relatively common autoimmune disease that results from the loss of immune tolerance to β-cell-associated antigens. Preclinical models have demonstrated the safety and efficacy of Tregs given in transplant rejection and autoimmune diseases such as T1D. Adoptive transfer of Tregs has been utilized in clinical trials for over a decade. However, the achievement of the adoptive transfer of Tregs therapy in clinical application remains challenging. In this review, we highlight the characterization of Tregs and compare the differences between umbilical cord blood and adult peripheral blood-derived Tregs. Additionally, we summarize conditional modifications in the expansion of Tregs in clinical trials, especially for the treatment of T1D. Finally, we discuss the existing technical challenges for Tregs in clinical trials for the treatment of T1D.
Topics: Adult; Humans; Diabetes Mellitus, Type 1; T-Lymphocytes, Regulatory; Fetal Blood; Autoimmune Diseases; Immune Tolerance
PubMed: 37544491
DOI: 10.1016/j.clim.2023.109716 -
Journal For Immunotherapy of Cancer Nov 2023γδ T cells are regarded as promising effector lymphocytes for next-generation cancer immunotherapies. In spite of being relatively rare in human peripheral blood, γδ... (Review)
Review
γδ T cells are regarded as promising effector lymphocytes for next-generation cancer immunotherapies. In spite of being relatively rare in human peripheral blood, γδ T cells are more abundant in epithelial tissues where many tumors develop, and have been shown to actively participate in anticancer immunity as cytotoxic cells or as "type 1" immune orchestrators. A major asset of γδ T cells for tackling advanced cancers is their independence from antigen presentation via the major histocompatibility complex, which clearly sets them apart from conventional αβ T cells. Here we discuss the main therapeutic strategies based on human γδ T cells. These include antibody-based bispecific engagers and adoptive cell therapies, either focused on the Vδ1 or Vδ2 γδ T-cell subsets, which can be expanded selectively and differentiated or engineered to maximize their antitumor functions. We review the preclinical data that supports each of the therapeutic strategies under development; and summarize the clinical trials being pursued towards establishing γδ T cell-based treatments for solid and hematological malignancies.
Topics: Humans; Receptors, Antigen, T-Cell, gamma-delta; Neoplasms; T-Lymphocyte Subsets; Intraepithelial Lymphocytes; Hematologic Neoplasms
PubMed: 38007241
DOI: 10.1136/jitc-2023-007955 -
Archives of Cardiovascular Diseases Jan 2024Cancer is associated with a hypercoagulable state and is a well-known independent risk factor for venous thromboembolism, whereas the association between cancer and... (Review)
Review
Cancer is associated with a hypercoagulable state and is a well-known independent risk factor for venous thromboembolism, whereas the association between cancer and arterial thromboembolism is less well established. Arterial thromboembolism, primarily defined as myocardial infarction or stroke is significantly more frequent in patients with cancer, independently of vascular risk factors and associated with a three-fold increase in the risk of mortality. Patients with brain cancer, lung cancer, colorectal cancer and pancreatic cancer have the highest relative risk of developing arterial thromboembolism. Antithrombotic treatments should be used with caution due to the increased risk of haemorrhage, as specified in current practice guidelines.
Topics: Humans; Stroke; Hemorrhage; Risk Factors; Myocardial Infarction; Venous Thromboembolism; Atrial Fibrillation; Neoplasms
PubMed: 38057257
DOI: 10.1016/j.acvd.2023.11.007 -
Journal of Immunology Research 2023Rheumatoid arthritis (RA) is a common chronic inflammatory autoimmune disease with a multifactorial etiology. Peripheral blood is the main channel of the immune system,...
BACKGROUND
Rheumatoid arthritis (RA) is a common chronic inflammatory autoimmune disease with a multifactorial etiology. Peripheral blood is the main channel of the immune system, and peripheral blood mononuclear cells (PBMCs) are the immune cells that initiate the autoimmune inflammatory process. However, there are few reports on the mechanisms of peripheral blood immunity in RA.
METHODS
ScRNA-seq was performed on four RA samples and integrated with single-cell transcriptome data from four healthy control samples downloaded from publicly available databases for analysis.
RESULTS
A total of 52,073 cells were used for descending clustering analysis to map RA peripheral blood immune cells at single-cell resolution. Redimensional clustering analysis of four major immune cells (T cells, monocytes, B cells, and natural killer cells) revealed that double-negative T (DNT) cells were significantly altered in abundance and function. And a number of genes (including SOCS3, cAMP-responsive element modulator (CREM), B2M, MTFP1, RSRP1, and YWHAB) were specifically downregulated in DNT cells. RA T cells, especially DNT cells, exhibit significant metabolic defects and dysfunction, mainly in the form of inhibition of oxidative phosphorylation, ATP synthesis, and major histocompatibility complex (MHC)-I-mediated antigen presentation. In addition, cellular communication networks were established, and it was evident that RA is significantly attenuated in the number and intensity of cellular communication. Monocytes and T cells play key roles in the process of the immune inflammatory response through CCL and MHC-related pathways.
CONCLUSIONS
This study describes the landscape of the peripheral blood immune system and cell communication in RA, characterizes the abundance of PBMCs, gene expression profiles, and changes in signaling pathways in RA patients, and identifies several key cell subpopulations (DNT and classic monocytes) and specific genes (SOCS3, CREM, B2M, MTFP1, RSRP1, and YWHAB). Meanwhile, we propose that classic monocytes in peripheral blood may migrate to sites of inflammation in synovial tissue under the chemotaxis of the chemokines CCL3 and CCL3L1, differentiate into macrophages, secrete proinflammatory cytokines, and thus participate in the inflammatory response. These findings provide new insights for the future elucidation of the peripheral blood immune mechanisms of RA and the search for new clinical therapeutic targets.
Topics: Humans; Leukocytes, Mononuclear; Single-Cell Gene Expression Analysis; Arthritis, Rheumatoid; Monocytes; Cell Communication
PubMed: 37600067
DOI: 10.1155/2023/6300633 -
Frontiers in Immunology 2023Vitiligo is a common autoimmune depigmented dermatology due to destruction of melanocytes. Much evidence suggests that vitiligo is associated with systemic immune...
BACKGROUND
Vitiligo is a common autoimmune depigmented dermatology due to destruction of melanocytes. Much evidence suggests that vitiligo is associated with systemic immune activation. Previous studies have focused on immune cell infiltration in and around lesion areas, but few studies have investigated the cell types and function of circulating immune cells in peripheral blood. Here, single cell RNA-sequencing (scRNA-seq) was used to investigate the mechanisms of peripheral immune responses in vitiligo patients.
METHODS
Peripheral blood was collected from five patients with progressive non-segmental vitiligo and three healthy controls. Peripheral blood mononuclear cells (PBMCs) were obtained by Ficoll-Paque density gradient centrifugation, and scRNA-seq was performed on isolated cell populations to obtain single cell transcriptomes and characterize important genes and intracellular signaling pathways. The key findings were validated with qPCR and flow cytometry assays.
RESULTS
We identified 10 major cell types by scRNA-seq. Among these cell types, neutrophils were specifically observed in our scRNA-seq data from PBMCs. Peripheral blood effector CD8+ T cells from vitiligo patients did not show significant differences at the transcriptome level compared with healthy controls, whereas regulatory T cells showed pro-inflammatory TH1-like properties. Innate immune cells, including natural killer cells and dendritic cells, showed increased antigen processing and presentation as well as upregulated interferon responses. B cells, monocytes, and neutrophils all showed activation. B cells, especially memory B cells, had upregulated expression of genes related to humoral immunity. Monocytes showed production of proinflammatory cytokines and chemokines. Neutrophils showed strong chemokine ligand-receptor (L-R) pair (CXCR8-CXCR2) autocrine signaling pathway.
CONCLUSION
This study revealed the genetic profile and signaling pathway characteristics of peripheral blood immune cells in vitiligo patients, providing new insights into its pathogenesis, which may facilitate identification of potential therapeutic targets.
Topics: Humans; Vitiligo; Leukocytes, Mononuclear; Gene Expression Profiling; T-Lymphocytes, Regulatory; Immunity
PubMed: 38077333
DOI: 10.3389/fimmu.2023.1221260 -
Cell Reports. Medicine Sep 2023Previous chemotherapy research has focused almost exclusively on apoptosis. Here, a standard frontline drug combination of cytarabine and idarubicin induces distinct...
Previous chemotherapy research has focused almost exclusively on apoptosis. Here, a standard frontline drug combination of cytarabine and idarubicin induces distinct features of caspase-independent, poly(ADP-ribose) polymerase 1 (PARP-1)-mediated programmed cell death "parthanatos" in acute myeloid leukemia (AML) cell lines (n = 3/10 tested), peripheral blood mononuclear cells from healthy human donors (n = 10/10 tested), and primary cell samples from patients with AML (n = 18/39 tested, French-American-British subtypes M4 and M5). A 3-fold improvement in survival rates is observed in the parthanatos-positive versus -negative patient groups (hazard ratio [HR] = 0.28-0.37, p = 0.002-0.046). Manipulation of PARP-1 activity in parthanatos-competent cells reveals higher drug sensitivity in cells that have basal PARP-1 levels as compared with those subjected to PARP-1 overexpression or suppression. The same trends are observed in RNA expression databases and support the conclusion that PARP-1 can have optimal levels for favorable chemotherapeutic responses.
Topics: Humans; Apoptosis; Cell Line; Leukemia; Leukocytes, Mononuclear; Poly(ADP-ribose) Polymerase Inhibitors
PubMed: 37683650
DOI: 10.1016/j.xcrm.2023.101191 -
Medicine Dec 2023Immune and inflammatory responses play an important role in tumorigenesis and metastasis. Inflammation is an important component of the tumor microenvironment, and the... (Review)
Review
Immune and inflammatory responses play an important role in tumorigenesis and metastasis. Inflammation is an important component of the tumor microenvironment, and the changes in inflammatory cells may affect the occurrence and development of tumors. Complete blood count at the time of diagnosis and treatment can reflect the inflammatory status within the tumor. Studies have shown that the number of certain inflammatory cells in peripheral blood and their ratios are important prognostic factors for many malignancies, including neutrophil, lymphocyte, monocyte, and platelet counts, as well as neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio, systemic immune-inflammation index, systemic inflammation response index and pan-immune-inflammation-value. The value of peripheral blood inflammation indexes in predicting the efficacy and prognosis of breast cancer neoadjuvant therapy is worth recognizing. This review details the application of peripheral blood inflammation indexes in the evaluation of efficacy and prediction of prognosis in neoadjuvant therapy for breast cancer, aiming to provide a more comprehensive reference for the comprehensive diagnosis and treatment of breast cancer.
Topics: Humans; Female; Lymphocytes; Blood Cell Count; Prognosis; Neutrophils; Blood Platelets; Inflammation; Breast Neoplasms; Retrospective Studies; Tumor Microenvironment
PubMed: 38050296
DOI: 10.1097/MD.0000000000036315