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Genetically engineered CD276-anchoring biomimetic nanovesicles target senescent escaped tumor cells to overcome chemoresistant and immunosuppressive breast cancer.

Chemotherapy-induced cellular senescence leads to an increased proportion of cancer stem cells (CSCs) in breast cancer (BC), contributing to recurrence and metastasis, while effective means to clear them are currently lacking. Herein, we aim to develop new approaches for selectively killing senescent-escape CSCs. High CD276 (95.60%) expression in multidrug-resistant BC cells, facilitates immune evasion by low-immunogenic senescent escape CSCs. CALD1, upregulated in ADR-resistant BC, promoting senescent-escape of CSCs with an anti-apoptosis state and upregulating CD276, PD-L1 to promote chemore

Tracking immune dysregulation in COVID-19: lymphocyte dynamics from hospitalization to recovery.

A hallmark of COVID-19 patients is the reduction of the lymphocyte population accompanied by activation, senescence, and exhaustion markers. We investigated patients admitted to hospital wards who either recovered after a short hospitalization or progressed to critical illness. Patients (n=48) were recruited between May and September 2020; 19 healthy volunteers were enrolled as controls. Blood samples were collected on days 0, 3, and 7 of hospitalization and around 30 days after discharge (convalescence sample, CS30). Lymphocyte counts and extended immunophenotyping were performed by flow cyto

Early T Cell Differentiation with Well-Maintained Function across the Adult Life Course in Sub-Saharan Africa.

Immune senescence is a significant contributor to health problems in the developed world and may be accelerated by chronic viral infections. To date, there have been few studies of immune function in healthy older people in sub-Saharan Africa. We assessed T cell and B cell phenotypes and immune responses to CMV, EBV, and influenza virus in Malawians aged 20-69 y. Notably, the proportion of naive (CCR7+CD45RA+) CD4 and CD8 T cells was only 14% of the lymphoid repertoire even in donors aged under 30 y but did not decrease further with age. A small increase in the late differentiated (CD27-CD28-)

Increased neutrophil senescence is associated with impaired immunosuppressive activity in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a complex pathogenesis that was previously thought to involve primarily adaptive immunity. Emerging evidence underscores the role of neutrophils in shaping immune dysregulation and inducing organ damage in lupus. This study aims to investigate the dynamics of neutrophil senescence and its relationship with lupus, an area that remains poorly understood. Here, we identify a significantly elevated proportion of CXCR4 hiCD62L lo senescence-like neutrophils in the peripheral blood of SLE patients compare to that in the hea

Immunotherapy for senescent cell clearance: Hallmarks, strategies and translational challenges.

Cellular senescence, a complex multifactorial process, is involved in the pathophysiology of various age-related diseases, such as cardiovascular disease and neurodegenerative disorders. Traditional interventions targeting single mechanisms yield limited efficacy. As a core hallmark and driver of aging, immunosenescence provides a critical target for precision interventions. This systematic review examines the hallmarks of aging, including cellular damage, epigenetic abnormalities, and immunosenescence. It highlights immunotherapy strategies targeting senescent cells, including CAR-T/NK cell t

Osteoimmune senescence in aging-related bone diseases.

Aging-related bone diseases are increasingly recognized as disorders in which uncoupled bone remodeling remains central but is substantially modified by immune-skeletal interactions. This review consolidates current evidence for osteoimmune senescence, a framework that links senescent skeletal cells, aging immune compartments, chronic SASP signaling, impaired immune clearance, and marrow-niche deterioration to reduced bone strength and repair. Osteoporosis, rheumatoid arthritis-associated erosion, osteoarthritis, periodontal bone loss, and delayed fracture healing are clinically distinct disea

Aging microenvironment and antitumor immunity for geriatric oncology: the landscape and future implications.

The tumor microenvironment (TME) has been extensively investigated; however, it is complex and remains unclear, especially in elderly patients. Senescence is a cellular response to a variety of stress signals, which is characterized by stable arrest of the cell cycle and major changes in cell morphology and physiology. To the best of our knowledge, senescence leads to consistent arrest of tumor cells and remodeling of the tumor-immune microenvironment (TIME) by activating a set of pleiotropic cytokines, chemokines, growth factors, and proteinases, which constitute the senescence-associated sec

Совпадение в полном тексте источника
… A T-cell senescence may be activated by soluble factors secreted by cancer cells, Tregs, and occur during the aging process. The senescence markers such as p16, SA-βGal are elevated, co-stimulatory receptors (CD27, CD28) are decreased and CD57 is increased. …

Pathological proliferation: a potential mechanism for poor CD4+ T cell recovery in people living with HIV.

BACKGROUND: People living with HIV (PLWH) fail to achieve normalization of CD4+ T cell counts and function, especially in immunological non-responders (INRs). The frequencies of Ki67+CD4+ T cells were inversely associated with CD4+ T cell counts in HIV infected patients. Early ART did not normalize CD4+ T cell proliferation. However, the features of the abnormal proliferation CD4+ T cell in INRs are far from known. METHOD: PLWH were divided into INRs (n= 16) and immunological responders (IRs, n= 53) groups. Mass cytometry was applied to peripheral blood T cells to profile the immune cells and

Differential alterations of the CD4 and CD8 T cell subsets in HIV-infected patients on highly active antiretroviral therapy with low CD4 T cell restoration.

OBJECTIVES: This study examined the homeostatic parameters possibly related to HIV-infected patients who, despite being under suppressive highly active antiretroviral therapy (HAART), show low-level CD4 T cell repopulation (LLR). METHODS: Twenty-one LLR individuals, 20 HIV-infected controls with satisfactory CD4 T cell repopulation (R) and 14 healthy subjects were studied. Markers related to activation, senescence and proliferation were analysed for both the CD4 and CD8 T cell subsets. Additionally, soluble CD14 (sCD14) and high-sensitivity C-reactive protein (hsCRP) were measured, and the CD

Allostatic stress load and CMV serostatus impact immune response to maximal exercise in collegiate swimmers.

Collegiate athletes are exposed to varying levels of academic and physical stressors, placing them at increased risk for stress-activated latent viral infections. However, the impact of allostatic stress load on the immune response to maximal exercise in athletes remains largely unknown. This study examined the effects of a 7-mo training period and cytomegalovirus (CMV) serostatus on immune cell response to high-intensity swim tests within a group of collegiate swimmers. Samples were collected from 15 National Collegiate Athletic Association Division I swimmers (9 men, 6 women: 19.87 ± 0.64 yr

Skipped BSCL2 Transcript in Celia's Encephalopathy (PELD): New Insights on Fatty Acids Involvement, Senescence and Adipogenesis.

OBJECTIVE: PELD (Progressive Encephalopathy with or without Lipodystrophy or Celia's Encephalopathy) is a fatal and rare neurodegenerative syndrome associated with the BSCL2 mutation c.985C>T, that results in an aberrant transcript without the exon 7 (Celia seipin). The aim of this study was to evaluate both the process of cellular senescence and the effect of unsaturated fatty acids on preadipocytes from a homozygous c.985C>T patient. Also, the role of aberrant seipin isoform on adipogenesis was studied in adipose-derived human mesenchymal stem cells. MATERIAL AND METHODS: Cellular senescenc

Genes associated with cellular senescence favor melanoma prognosis by stimulating immune responses in tumor microenvironment.

PURPOSE: Skin cutaneous melanoma (SKCM), a malignant tumor from melanocytes, is the fifth most prevalent tumor. Immune checkpoint inhibitor (ICI) immunotherapy improves prognosis of SKCM, but immune response varies for different populations. Cellular senescence in the tumor microenvironment (TME) promotes antitumor immunity, mediated by dendritic cells (DC) and CD8+ T cells. Therefore, we sought to explore the role of cellular senescence in the TME of SKCM through bioinformatics and machine learning. METHODS: First, we obtained 93 cellular senescence-prognosis genes (CSPGs) by univariate surv

Roles of Menin in T cell differentiation and function: Current knowledge and perspectives.

The commitment to specific T lymphocytes (T cell) lineages is governed by distinct transcription factors, whose expression is modulated through epigenetic mechanisms. Unravelling these epigenetic mechanisms that regulate T cell differentiation and function holds significant importance for understanding T cells. Menin, a multifunctional scaffolding protein, is implicated in various cellular processes, such as cell proliferation, cell cycle control, DNA repair and transcriptional regulation, primarily through epigenetic mechanisms. Existing research indicates Menin's impact on T cell differentia

Proliferation capacity and cytotoxic activity are mediated by functionally and phenotypically distinct virus-specific CD8 T cells defined by interleukin-7R{alpha} (CD127) and perforin expression.

Cytotoxicity and proliferation capacity are key functions of antiviral CD8 T cells. In the present study, we investigated a series of markers to define these functions in virus-specific CD8 T cells. We provide evidence that there is a lack of coexpression of perforin and CD127 in human CD8 T cells. CD127 expression on virus-specific CD8 T cells correlated positively with proliferation capacity and negatively with perforin expression and cytotoxicity. Influenza virus-, cytomegalovirus-, and Epstein-Barr virus/human immunodeficiency virus type 1-specific CD8 T cells were predominantly composed o

The Proportion of Memory CD8+ T Cell Predicts Infection Event in Patients with Peritoneal Dialysis.

INTRODUCTION: The immune senescence marked by the inflation of memory T cell is established in end-stage renal disease (ESRD) patients with peritoneal dialysis (PD). These patients suffer high incidence of infectious disease, which has been relevant to immune dysfunction. However the association of immune senescence with infection in PD patients is not clear. This prospective study aimed to investigate the relationship between proportion of T cell subsets and infection event in patients on PD. METHODS: We enrolled patients on PD >6 months from January 1, 2016 to December 30, 2016 and followed

Bioinformatics-based discovery of intervertebral disc degeneration biomarkers and immune-inflammatory infiltrates.

BACKGROUND: Intervertebral disc degeneration (IVDD) is a common chronic disease in orthopedics, and its molecular mechanisms are still not well explained. AIM: This study's objective was to bioinformatics-based discovery of IVDD biomarkers and immune-inflammatory infiltrates. MATERIALS AND METHODS: The IVDD illness gene collection was gathered from GeneCards, DisGeNet, and gene expression profiles were chosen from the extensive Gene Expression Omnibus database (GSE124272, GSE150408, and GSE153761). The STRING database was used to create a network of protein-protein interactions, while the Ky

Single-Cell Transcriptome Reveals the Heterogeneity of T Cells in Mice with Systemic Lupus Erythematosus and Neuronal Inflammation.

INTRODUCTION: Systemic lupus erythematosus is a heterogeneous autoimmune disease. A burst of autoimmune reactions in various systems can lead to severe clinical conditions closely associated with mortality. T cells serve as mediators that drive the occurrence and maintenance of inflammatory processes. METHODS: In this work, we employed single-cell transcriptome sequencing (scRNA-seq) involving 27704 cells from the brain and spleen tissues of MRL/lpr mice and 25355 healthy controls from BALB/c mice to explore the heterogeneity of T cells and their migration from the spleen to the brain. RESUL

Targeting p21-High Senescent Kupffer Cells Nanotherapeutically Potentiates Antitumor Immunity in Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombus.

Hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) are associated with a significantly poor prognosis and limited treatment options. Single-cell RNA sequencing (scRNA-seq) has revealed senescent Kupffer cells (sKCs), which are characterized by high levels of p21 expression and enriched in the tumor microenvironment (TME) of HCC-PVTT. These sKCs exhibit a pronounced senescence-associated secretory phenotype (SASP), promoting the proliferation and invasion of tumors and crosstalk with cancer-associated fibroblasts. To target sKCs, a biomimetic nanodelivery system term

Non-Engineered Physiologically Modulated Nanovesicles Augment Antitumor Immune Responses via Dual-Pathway T Cell Activation.

The therapeutic efficacy of cancer vaccines is critically contingent upon CD8+ T cell-mediated antitumor immunity, but the effectiveness is hindered due to insufficient T cell activation. Inspired by the close interplay between cellular physiological states and immunoregulatory functions, we propose ASCENT, a nanovaccine platform integrating nanovesicles derived from activated platelets and senescent tumor cells to naturally co-present antigens and co-stimulatory molecules, thereby enabling dual-pathway T cell activation. Specifically, senescent tumor cells promote antigen presentation via upr

Development and Validation of Novel Senescence-TIME Biomarkers for Predicting the Prognosis and Immunotherapy Responsiveness of SKCM Patients.

BACKGROUND: Increasing evidence indicates that tumor cellular senescence can impair antitumor immunity and promote skin cutaneous melanoma (SKCM) progression. However, effective methods for assessing tumor cellular senescent status and tumor immune microenvironment (TIME) status remain lacking. This study intends to establish a novel Senescence-TIME Risk Score (STIRS) based on senescence and TIME related genes to predict prognosis and immunotherapy responsiveness in SKCM patients, thereby providing new strategies for current clinical personalized treatment. METHODS: We identified distinct sen