Dia-B-Ties: B Cells in the Islet–Immune-Cell Interface in T1D

Biomolecules, Journal Year: 2025, Volume and Issue: 15(3), P. 332 - 332

Published: Feb. 25, 2025

Type 1 diabetes (T1D) is an autoimmune disease that affects estimated 30 million people worldwide and results in a lifelong dependency of exogenous insulin treatments. While T1D characterized by T-cell driven-destruction the insulin-secreting β cells, B lymphocytes play key role islet–immune interface. cells are essential intermediary between islet other immune-cell populations. Through antigen presentation, cytokine secretion, antibody production, activating autoreactive islet-specific T thus potentiating pancreatic inflammation early stages T1D. Despite this, their development remains understudied feature with significant therapeutic potential. Herein, we will discuss current knowledge islet–immune-cell interface within through lens lymphocytes. We also consider gaps may be limiting further opportunities.

Language: Английский

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Multifaceted function of B cells in tumorigenesis

Frontiers of Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: March 22, 2025

Language: Английский

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Dynamics of tertiary lymphoid structures and immune cross talk in early versus advanced colorectal cancer: potential implications for immunotherapy

Cancer Immunology Immunotherapy, Journal Year: 2025, Volume and Issue: 74(6)

Published: April 26, 2025

Abstract Background Irrespective of microsatellite status, immune checkpoint inhibitor therapy shows superior efficacy in early-stage colorectal cancer (CRC) compared to advanced cases. The distinctions the tumor microenvironment (TME) and tertiary lymphoid structure (TLS) between early- advanced-stage CRC may represent a critical factor, yet remain incompletely elucidated. Methods We comprehensively analyzed single-cell RNA sequencing data, bulk transcription data pathological tissue investigate dynamic changes TME. features TLS tumors their potential impact on immunotherapy were explored using three in-house cohorts. Results provided fine maps landscape early CRC. Significant functional differences identified CD4 + Tfh BGC cells revealed CXCL13 expression CD8 Tex cells, along with CD40–CD40L interactions could be key regulators functionality subsequently affect response immunotherapy. Conclusions Our research shed light multilayered dysfunction elucidates alterations during progression CRC, providing insights for studies exploration target

Language: Английский

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Single-cell spatial transcriptomics of tertiary lymphoid organ-like structures in human atherosclerotic plaques

Nature Cardiovascular Research, Journal Year: 2025, Volume and Issue: unknown

Published: April 28, 2025

Language: Английский

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Efficacy, safety and single-cell analysis of neoadjuvant immunochemotherapy in locally advanced oral squamous cell carcinoma: a phase II trial

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 28, 2025

Language: Английский

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Decreased AMPK/SIRT1/PDK4 induced by androgen excess inhibits human endometrial stromal cell decidualization in PCOS

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: July 30, 2024

Polycystic ovary syndrome (PCOS) is a complex common endocrine disorder affecting women of reproductive age. Ovulatory dysfunction recognized as primary infertile factor, however, even when ovulation medically induced and restored, PCOS patients continue to experience reduced cumulative pregnancy rates higher spontaneous miscarriage rate. Hyperandrogenism, hallmark feature PCOS, affects ovarian folliculogenesis, endometrial receptivity, the establishment maintenance pregnancy. Decidualization denotes transformation that stromal compart endometrium must undergo accommodate pregnancy, driven by rising progesterone levels local cAMP production. However, studies on impact hyperandrogenism decidualization are limited. In this study, we observed cells from with exhibit abnormal responses during in vitro decidualization. A high concentration testosterone inhibits human (HESCs) RNA-Seq analysis demonstrated pyruvate dehydrogenase kinase 4 (PDK4) expression was significantly lower compared those without hyperandrogenism. We also characterized PDK4 elevated stroma at mid-secretory phase. Artificial could enhance expression, while downregulation leads both vivo vitro. Mechanistically, excess IGFBP1 PRL followed phosphorylating AMPK stimulates expression. Based co-immunoprecipitation analysis, an interaction between SIRT1 PDK4, promoting glycolysis facilitate Restrain AR activation resumes AMPK/SIRT1/PDK4 pathway suppressed excess, indicating primarily acts through stimulation. Androgen disrupting signaling pathway. These data demonstrate critical roles regulating provide valuable information for understanding underlying mechanism

Language: Английский

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Premalignant Progression in the Lung: Knowledge Gaps and Novel Opportunities for Interception of Non-Small Cell Lung Cancer. An Official American Thoracic Society Research Statement

American Journal of Respiratory and Critical Care Medicine, Journal Year: 2024, Volume and Issue: 210(5), P. 548 - 571

Published: Sept. 1, 2024

Despite significant advances in precision treatments and immunotherapy, lung cancer is the most common cause of death worldwide. To reduce incidence improve survival rates, a deeper understanding premalignancy multistep process tumorigenesis essential, allowing timely effective intervention before development.

Language: Английский

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Sintilimab in combination with stereotactic body radiotherapy and granulocyte-macrophage colony-stimulating factor in metastatic non-small cell lung cancer: The multicenter SWORD phase 2 trial

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 22, 2024

This single-arm, multicenter, phase 2 trial (NCT04106180) investigated the triple combination of sintilimab (anti-PD1 antibody), stereotactic body radiotherapy (SBRT) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in metastatic non-small cell lung cancer (NSCLC). With a median follow-up 32.1 months, 18 (36.7%, 90% CI 25.3%–49.5%) 49 evaluable patients had an objective response, meeting primary endpoint. Secondary endpoints included out-of-field (abscopal) response rate (ASR), progression-free survival (PFS), overall (OS), treatment-related adverse events (TRAEs). The ASR was 30.6% (95% 18.3%–45.4%). PFS OS were 5.9 2.5–9.3) 18.4 9.7–27.1) respectively. Any grade 3 TRAEs occurred 44 (86.3%) 6 (11.8%) patients, without 4–5 TRAEs. Moreover, pre-specified biomarker analyses, SBRT-induced increase follicular helper T cells (Tfh) unirradiated tumor lesions patient's blood, as well circulating IL-21 levels, found associated with improved prognosis. Taken together, therapy tolerated promising efficacy Tfh may play critical role SBRT-triggered anti-tumor immunity NSCLC. Combinations immune checkpoint inhibitors have been explored for treatment Here authors report results (anti-PD1) GM-CSF

Language: Английский

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NLRP12/C1qA positive feedback in tumor-associated macrophages regulates immunosuppression through LILRB4/NF-κB pathway in lung adenocarcinoma

Cancer Immunology Immunotherapy, Journal Year: 2024, Volume and Issue: 74(1)

Published: Nov. 11, 2024

The anti-tumor immune response is greatly hindered by the protumor polarization of tumor-associated macrophages (TAMs). Cancer-related inflammation plays a central role in TAMs polarization. Our study explored unique positive feedback loop between inflammasome and complement TAMs. present identified NOD-like receptors family pyrin domain containing 12 (NLRP12) formed with C1qA drove via LILRB4/NF-κB pathway. In addition, NLRP12 was predominantly expressed associated poorer prognosis lung adenocarcinoma (LUAD) patients. Knocking down LILRB4 inhibited NLRP12-overexpressing promoted tumor cells' malignant progression T proliferation cytotoxic function. Lastly, knockout (NLRP12−/−) reversed macrophage polarization, enhanced T-cell immunity, suppressed growth. findings highlighted essential NLRP12/C1qA pathway promoting Inhibition development response. may be promising target for LUAD immunotherapy.

Language: Английский

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Global trends in tertiary lymphoid structures: a bibliometric analysis from 2014 to 2023

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 15, 2024

Aim and background Tertiary lymphoid structures (TLS) are increasingly recognized for their role in immunity. Despite growing interest, a systematic bibliometric analysis of TLS-related research has been lacking. To provide comprehensive overview current trends hotspots, we conducted using data from the Web Science Core Collection. Methods We retrieved publications Citation Index Expanded within Collection January 2014 to December 2023. Co-occurrence with “VOSviewer” identified status while “CiteSpace” was used co-citation assess knowledge evolution bursts. Thematic explored bibliometrics identify emerging keyword trends. Additionally, examined country/region, institutional, author contributions collaborations. Tables were created Microsoft Word. Results A total 785 analyzed, showing continuous growth trend 2017 2023, indicating escalating interest TLS among researchers. Leading countries China (231 publications), United States (212 France (89 publications). The most productive institution “Institut national de la santé et recherche médicale” (70 publications) Catherine Sautes-Fridman (21 respectively. Key topics included TLS, B cells, immunotherapy. Recent focused on mechanisms linking cancers, such as immunotherapy, tumor microenvironment, tumor-infiltrating lymphocytes, prognosis, immune checkpoint inhibitors, highlighting an expanding area study. TLS’ potential biomarker predicting immunotherapy efficacy across different cancer types remains burgeoning direction. Conclusions This study provides global publications, revealing key literature metrics identifying influential articles concerns. These findings contribute valuable insights into suggest future directions this dynamic field.

Language: Английский

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