Nuclear Molecular Imaging for Evaluating T Cell Exhaustion DOI
Huimin Zhou,

Guangfa Bao,

Jun Zhao

и другие.

Molecular Pharmaceutics, Год журнала: 2024, Номер 22(1), С. 103 - 112

Опубликована: Ноя. 25, 2024

T cells are indispensable for the therapeutic efficacy of cancer immunotherapies, including immune checkpoint blockade. However, prolonged antigen exposure also drives into exhaustion, which is characterized by upregulated inhibitory molecules, impaired effector functions, reduced cytotoxicity, altered metabolism, etc. Noninvasive monitoring cell exhaustion allows a timely identification patients that most likely to benefit from immunotherapies. In this Review, we briefly explain biological cascades underlying modulation present concise update on nuclear molecular imaging tracers and then discuss potential opportunities future development.

Язык: Английский

Tissue-resident memory T-cell expressions and their prognostic role in head and neck squamous cell carcinoma: a systematic review and meta-analysis DOI Creative Commons
Anwar Ali,

Muhammad Furqan Bari,

Saba Arshad

и другие.

BMC Cancer, Год журнала: 2025, Номер 25(1)

Опубликована: Фев. 26, 2025

CD8 + tissue-resident memory T lymphocytes (TRM) are a subset of tumor-infiltrating (TILs) that mediate innate immunity. Clinically, they can prevent tumor development, growth and metastasis play potential role in immunosurveillance long-term immunity head neck squamous cell carcinoma (HNSCC). This systematic review meta-analysis aimed to assess the prognostic significance TRM cells, identified by key immunophenotypic markers CD103, CD69, CD49a linked patient outcomes such as overall survival (OS) HNSCC its specified subcategory, OSCC. PubMed, Scopus, Web Science databases were searched systematically include original research articles comprising cross-sectional, observational, experimental studies, clinical trials. The characteristics studies recorded for years publication, design, cancer types, HPV status, staging, diagnostic assays, markers, immune response regulators. Hazard ratios (HR) with confidence intervals (CI) p-values extracted observing association between and/or exhibiting cytotoxic potential. proportion cells co-expressing was estimated extracting actual percentage expression TME from graphical presentation data included studies. Among 276 11 reviewing abstract or title full-text articles. findings these demonstrated strong characterized improved OS patients HNSCC, subtype, Notably, similar trends observed within relative oropharyngeal carcinomas (OPSCC), another recognized subtype HNSCC. pooled HR 0.49 (95% CI: 0.23–1.02, p < 0.001), indicating benefit infiltration related subtypes OSCC OPSCC. However, at aggregate incidences not statistically significant (p > 0.05). Increased expressing is associated better prognosis registered international database protocols https://www.crd.york.ac.uk/prospero/ under protocol identifier: CRD42024570177.

Язык: Английский

Процитировано

0

Blood-brain barrier crossing biopolymer activates immunity in primary brain lymphoma by targeting c-Myc and α-PD-1: Artificial intelligence analysis DOI
Vladimir A. Ljubimov, Tao Sun, Jiawei Wang

и другие.

Journal of Controlled Release, Год журнала: 2025, Номер unknown, С. 113611 - 113611

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0

Single-cell and spatial analyses reveal the effect of VSIG4+S100A10+TAMs on the immunosuppression of glioblastoma and anti-PD-1 immunotherapy DOI
Ziyuan Liu, Yufan Yang,

Yiqi Fan

и другие.

International Journal of Biological Macromolecules, Год журнала: 2025, Номер unknown, С. 142415 - 142415

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0

The Impact of Mast Cells on the Anatomy, Cellular Communication, and Molecular Immune Network of Lymph Nodes DOI Creative Commons
Daniel Elieh Ali Komi, Marcus Maurer, Frank Siebenhaar

и другие.

Clinical Reviews in Allergy & Immunology, Год журнала: 2025, Номер 68(1)

Опубликована: Апрель 2, 2025

Lymph nodes (LNs) are ovoid-shape capsulated structures interposed along the lymphatic vessels. Owing to their unique architecture, LNs place immune cell types in distinct compartments allowing effective contact of antigens them. Their efficient function results concentration and bridging antigen-presenting cells like DCs B adaptive immunity (circulating T lymphocytes remaining monitor antigens) coordinate responses. In a healthy LN, primarily clustered lymphoid follicles, whereas organized deeper paracortex region. Mast (MCs) among cells; normal presence or pathologic infiltration has been reported LNs. MCs enter through afferent vessels can be found all compartments, ranging from subcapsular sinus deepest sections medullary sinus; however, they commonly zone but rarely follicles. pathologies with LN involvement solid tumors, features MC accumulation anatomical region within differ based on type tumor organ. Moreover, may influence trafficking other out facilitate migration into which is crucial for orchestrating responses, especially vaccination; moreover, play role induction peripheral tolerance. MC-released mediators including TNF tissue-resident tryptase LN-MCs mediate hyperplasia extension vasculature, respectively. support lymphangiogenesis by releasing VEGF-C VEGF-D vivo. Further research anticipated due development pharmaceuticals that impact survival inhibit activation. this review, we summarize current literature regarding outcomes focus MC-mediated responses two categories: direct cell-to-cell mediator-based interactions.

Язык: Английский

Процитировано

0

miR-23a-mediated TRF2 repression in CD4 T cells from PLWH DOI Creative Commons
Lam Nhat Nguyen, Juan Zhao,

Jaeden S. Pyburn

и другие.

Molecular Immunology, Год журнала: 2025, Номер 182, С. 107 - 116

Опубликована: Апрель 19, 2025

CD4 T cells in people living with HIV (PLWH) on antiretroviral therapy (ART) often exhibit an inflammaging phenotype, characterized by persistent inflammation, immune activation, exhaustion, senescence, and apoptosis. We have previously demonstrated that inhibition of telomeric repeat factor 2 (TRF2) protein causes accelerated telomere erosion premature cell aging PLWH. In this study, we further investigated how TRF2 is inhibited from PLWH, focusing the miRNA-mediated mechanism. found miR-23a significantly increased, whereas repressed, PLWH compared to healthy subjects (HS). Bioinformatics analysis revealed 3'UTR a potential target miR-23a. Co-transfection luciferase construct containing into HEK293T suppresses translation. Notably, receptor (TCR) activation both HS increased decreased expression. Furthermore, increasing led decrease level increase cellular apoptosis - phenotype similar what observed Moreover, knockdown TRF2, but not TRF1, levels. These results suggest negatively regulates expression cells; thus, targeting may level, thereby protect integrity restore functions

Язык: Английский

Процитировано

0

Downexpression of miR- 17 - 5p and miR- 125a- 5p is Potentially Associated with the Renal Impairment Through STAT- 3 and CD69 in Multiple Myeloma Adult Patients DOI
Riham Abdel‐Hamid Haroun, Soad M. Eweida, Dina Samir Elsaid

и другие.

Biochemical Genetics, Год журнала: 2025, Номер unknown

Опубликована: Апрель 23, 2025

Язык: Английский

Процитировано

0

HDAC6 Deletion Decreases Pristane-induced Inflammation DOI Creative Commons

Dao Xu,

Xin Luo, Christopher M. Reilly

и другие.

ImmunoHorizons, Год журнала: 2024, Номер 8(9), С. 668 - 678

Опубликована: Сен. 1, 2024

Abstract Systemic lupus erythematosus is an autoimmune disease characterized by excessive inflammation and production of pathogenic Abs. Histone deacetylase 6 (HDAC6) a class IIb histone deacetylase. It has been reported that selective HDAC6 inhibition decreases in mouse models. In this study, sex- age-matched wild-type (WT) HDAC6−/− mice on the C57BL/6 background were administered 0.5 ml pristane or PBS i.p. at 8–12 wk age euthanized 10 d later. At sacrifice, body weight spleen measured, sera collected, splenocytes peritoneal cells harvested for flow cytometry. We found administration increased with no difference between WT mice. Pristane promoted population CD11b+Ly6C++ inflammatory monocytes CD11b+Ly6G+ neutrophils. Peritoneal recruitment these neutrophils was significantly decreased compared Flow cytometry results showed number CD69+ T B also induced IFN signature genes as determined RT-qPCR. Furthermore, not affected vitro studies J774A.1 revealed inhibitor (ACY-738) acetylation NF-κB while increasing Stat1 phosphorylation, which resulted inducible NO synthase LPS/IFN-γ–stimulated cells. Taken together, demonstrate although may inhibit some pathways, others remain unaffected.

Язык: Английский

Процитировано

1

High percentage of bone marrow CD8+ tissue-resident-like T cells predicts inferior survival in patients with acute myeloid leukemia DOI Creative Commons
Letong Cai, Wenpu Lai, Danlin Yao

и другие.

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Фев. 27, 2024

Abstract Background Acute myeloid leukemia (AML) is a malignant clonal blood disease and the most common type of acute in adults. Despite continuous advances treatments, long-term prognosis AML has not improved substantially. Tissue-resident memory T cells (TRMs) infiltrating solid tumors could influence tumor progression response to immune therapies; however, proportion prognostic significance TRMs bone marrow (BM) patients with are unclear. Methods We use flow cytometry assay phenotypic 49 BM samples from newly diagnosed (ND-AML). The Kaplan–Meier Plotter database verified relationship between expression CD8 + TRM-like cell characteristic genes (CD8A, CD69, TOX) patient survival. Additionally, further explored existence function by analyzing single proteo-genomic dataset healthy. Results found that effector (TEM) highly expressed CD69 (CD8 cells), their number significantly increased ND-AML compared HIs. high subset associated poor overall survival rate was reduced, especially M4 M5 subtypes. Phenotypic analysis revealed subpopulation exhibited exhausted characteristics, but its CD27 CD28 low CD57 suggest proliferative potential. single-cell proteogenomic confirmed checkpoints costimulatory molecules. Conclusions accumulation be considered as an related prediction marker for AML. Although mechanisms driving escape remains unknown, we believe targeted reversal this through checkpoint inhibitors another immune-related “brake” may benefit some

Язык: Английский

Процитировано

0

High percentage of bone marrow CD8+ tissue-resident-like memory T cells predicts inferior survival in patients with acute myeloid leukemia DOI Creative Commons
Letong Cai, Wenpu Lai, Danlin Yao

и другие.

Blood Science, Год журнала: 2024, Номер 6(3), С. e00194 - e00194

Опубликована: Июнь 6, 2024

Tissue-resident memory T (TRM) cells infiltrating solid tumors could influence tumor progression and the response to immune therapies. However, proportion prognostic value of TRM in bone marrow (BM) patients with acute myeloid leukemia (AML) are unclear. In this study, we used flow cytometry assay phenotype 49 BM samples from newly diagnosed AML (ND-AML). We found that CD8 + effector (TEM) highly expressed CD69 (CD8 TRM-like cells), their percentage was significantly increased ND-AML compared healthy individuals (HI). The high subset associated poor overall survival our cohort. Kaplan–Meier Plotter database verified a reduced rate among expression cell characteristic genes ( CD8A , TOX ), especially M4 M5 subtypes. Phenotypic analysis revealed subpopulation exhibited exhausted characteristics, but its CD27 CD28 low CD57 suggested proliferative potential. single-cell proteogenomic dataset confirmed existence checkpoints costimulatory molecules. conclusion, accumulation be an immune-related prediction marker for AML.

Язык: Английский

Процитировано

0

Regulating Human T Lymphocytes Through Magnetogenetic Tools DOI Open Access
Seyed Hossein Helalat,

Rodrigo Coronel Téllez,

Helga Thora Kristinsdóttir

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Окт. 12, 2024

Abstract The field of synthetic biology has expanded the possibilities for controlling cellular functions, particularly in development mammalian cells therapeutic applications. This study explored application magnetogenetic tools to regulate T cell activity, a crucial aspect developing advanced immunotherapies. Magnetogenetic use magnetic fields remotely control engineered ion channels and protein domains, providing non-invasive, deep-tissue stimulation that overcomes limitations traditional methods. We investigated effects three - TRPV1 (TRP1-Fer) TRPV4 (TRP4-Fer) channels, Electromagnetic Perceptive Gene (EPG) Jurkat cells. First, calcium concentration measurements confirmed activity these within Using qPCR proteomics analysis, we then analyzed their impact on activation, signaling, mitochondrial function, membrane integrity, gene expression under both stimulated (with antigens) non-stimulated conditions. Our results revealed significant upregulation activation calcium-handling proteins cells, indicating enhanced cytoskeletal dynamics compared controls. However, unexpectedly led deactivation investigation showed while induction alone deactivated antigen conjunction with amplified activation. highlights potential magnetogenetics precisely modulate presenting promising avenues more effective controlled findings also underscore need careful optimization mitigate adverse integrity function.

Язык: Английский

Процитировано

0