It’s about TIME – Gal-9 as a potential immunotherapeutic target in pancreatic ductal adenocarcinoma

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Янв. 31, 2025

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, characterized by an extremely poor prognosis and limited therapeutic options. Central to progression immune evasion PDAC is tumor (immune) microenvironment (TIME), where checkpoint proteins such as galectin-9 (Gal-9) play pivotal roles. Gal-9 significantly contributes immunosuppressive milieu interacting with various cells, T macrophages, myeloid-derived suppressor cells (MDSCs). These interactions suppress anti-tumor immunity, thus facilitating growth metastasis. This review comprehensively examines multifaceted role in TIME PDAC, detailing its mechanisms action, including induction regulatory polarization tumor-associated modulation apoptotic pathways via Tim-3 caspase activation. The potential targeting Gal-9, either alone or combination other inhibitors anti-PD-L1, also discussed, highlighting preclinical findings that suggest promising avenues for enhancing responses. By elucidating complex biological activities within TIME, this underscores importance innovative strategies aimed at mitigating effects PDAC.

Язык: Английский

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Purification and characterization of lectin from Phyllanthus reticulatus (PRL) plant fruit inducing cytotoxic effect on T47D and SKBR3 breast cancer cell lines

International Journal of Biological Macromolecules, Год журнала: 2025, Номер 307, С. 142006 - 142006

Опубликована: Март 12, 2025

Язык: Английский

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Genome-wide CRISPR screen identifies IRF1 and TFAP4 as transcriptional regulators of Galectin-9 in T cell acute lymphoblastic leukemia

Science Advances, Год журнала: 2025, Номер 11(12)

Опубликована: Март 19, 2025

Galectin-9 is overexpressed in a variety of cancers and associated with worse clinical outcome some cancers. However, the regulators driving expression are unknown. Here, we defined transcriptional epigenetic circuitry pediatric T cell acute lymphoblastic leukemia (T-ALL), as an example disease strong expression, which higher was lower overall survival. By performing genome-wide CRISPR screen, identified transcription factors IRF1 TFAP4 key for by binding its regulatory elements. Whereas observed exclusively on promoter, detected at enhancer solely T-ALL cells levels. Together, our results show that responsible indispensable further fine-tunes expression. Our approach, flow-based screen complemented factor mapping, creates innovative opportunities understanding manipulating regulation cancer.

Язык: Английский

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“Galectin-9: A double-edged sword in Acute Myeloid Leukemia”

Annals of Hematology, Год журнала: 2025, Номер unknown

Опубликована: Май 9, 2025

Acute Myeloid Leukemia (AML) presents a formidable challenge in the realm of hematologic malignancies, characterized by unregulated proliferation myeloid progenitor cells, leading to severe disruptions normal hematopoiesis. This review examines multifaceted role Galectin-9, crucial glycan-binding protein pathophysiology AML, emphasizing its potential as both prognostic biomarker and therapeutic target. Recent insights into molecular underpinnings particularly those involving genetic mutations cytogenetic abnormalities, illuminate complex landscape this disease, where patient outcomes are significantly influenced individual biological markers. initially recognized for involvement fundamental processes such cell immune modulation, has emerged pivotal molecule with expression levels correlating leukemic behavior clinical prognosis. consolidates extensive literature on elucidating transformation implications manipulating pathway. By investigating intricate relationship between Galectin-9 we aim provide comprehensive understanding that could lead innovative strategies managing aggressive malignancy, offering hope improved survival through targeted interventions.

Язык: Английский

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IFN-α and vitamin B6-induced galectin-9 promotes the immunomodulatory function of human clonal mesenchymal stem cells

Stem Cell Research & Therapy, Год журнала: 2025, Номер 16(1)

Опубликована: Май 30, 2025

Mesenchymal stem cells (MSCs) possess a variety of immunomodulatory functions that can vary depending on the MSC line. Investigating priming strategies is essential for increasing potential MSCs. Human clonal MSCs (cMSCs) were primed with TNF-α, IFN-γ, IL-1β, IFN-α, and vitamin B6. Their functions, including T-cell proliferation cytokine production, analyzed. The cMSCs injected intravenously into mouse model ovalbumin-induced atopic dermatitis (AD), their therapeutic effects evaluated. We identified IFN-α B6 as promising agents when they are combined TNF-α IFN-γ. showed expression galectin-9 (Gal-9), IL-1Ra, PDL-1. Gal-9 facilitates induction regulatory T (Tregs) apoptosis. Treatment significantly alleviated pathological changes in an AD model. Notable improvements included reduction epidermal thickness (p < 0.05), decreased number mast eosinophils dermis 0.01), restored claudin-1 epidermis 0.0001), lower serum levels IgE 0.05). This novel combination factors promotes by inducing Gal-9. Consequently, may serve excellent biomarker screening capabilities, facilitating more accurate assessment effectiveness.

Язык: Английский

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Secretome and immune cell attraction analysis of head and neck cancers

Cancer Immunology Immunotherapy, Год журнала: 2024, Номер 73(11)

Опубликована: Сен. 9, 2024

Язык: Английский

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Immunomodulation by galectin-9: Distinct role in T cell populations, current therapeutic avenues and future potential

Cellular Immunology, Год журнала: 2024, Номер 407, С. 104890 - 104890

Опубликована: Ноя. 13, 2024

Galectins, glycan-binding proteins, have been identified as critical regulators of the immune system. Recently, Galectin-9 (Gal-9) has emerged biomarker that correlates with disease severity in a range inflammatory conditions. However, Gal-9 highly different roles context immunoregulation, potential to either stimulate or suppress response. Neutralizing antibodies targeting developed and are early test phase investigating their therapeutic cancer. Despite ongoing research, mechanisms behind action remain not fully understood, extrapolating implications this molecule from previous studies is challenging. Here, we examine pleiotropic function focusing on conventional T lymphocytes, providing current overview its immunostimulatory immunosuppressive roles. In particular, highlight differentially regulates responses depending context. Considering complexity, further investigation Gal-9's intricate biology necessary define strategies disorders cancer treatment aimed at inducing inhibiting signaling.

Язык: Английский

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TGFB2 mRNA Levels Prognostically Interact with Interferon-Alpha Receptor Activation of IRF9 and IFI27, and an Immune Checkpoint LGALS9 to Impact Overall Survival in Pancreatic Ductal Adenocarcinoma

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(20), С. 11221 - 11221

Опубликована: Окт. 18, 2024

The treatment of pancreatic ductal adenocarcinoma (PDAC) is an unmet challenge, with the median overall survival rate remaining less than a year, even use FOLFIRINOX-based therapies. This study analyzed archived macrophage-associated mRNA expression using datasets deposited in UCSC Xena web platform to compare normal tissue and PDAC tumor samples. TGFB2 gene exhibited low levels tissue, one TPM. In contrast, 7.9-fold increase relative (p < 0.0001). Additionally, components type-I interferon signaling pathway significant upregulation including Interferon alpha/beta receptor 1 (IFNAR1; 3.4-fold increase, p 0.0001), regulatory factor 9 (IRF9; 4.2-fold Signal transducer activator transcription (STAT1; 7.1-fold Alpha Inducible Protein 27 (IFI27; 66.3-fold We also utilized TCGA cBioportal KMplotter relate outcomes. These increased were found be prognostically significant, whereby patients high either TGFB2, IRF9, or IFI27 showed OS times ranging from 16 20 months 0.01 compared 72 for both IRF9 IFI27). Examination database determined prognostic impact by comparing expressing versus (50th percentile cut-off) macrophage TME. TME levels, significantly shorter outcomes (Median 15.3 72.7 months, Furthermore, multivariate Cox regression models applied control age at diagnosis. Nine genes increases hazard ratios expression, marker interaction term between (mRNA markers: C1QA, CD74, HLA-DQB1, HLA-DRB1, HLA-F, IFI27, LGALS9, MARCO). results our suggest that combination pharmacological tools can used treating patients, targeting pathway. statistical nine suggests negative indicator IFN-I activated TAM immune checkpoint LGALS9 (upregulated 16.5-fold tissue;

Язык: Английский

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Unravelling the Reasons Behind Limited Response to Anti-PD Therapy in ATC: A Comprehensive Evaluation of Tumor-Infiltrating Immune Cells and Checkpoints

Endocrine Pathology, Год журнала: 2024, Номер unknown

Опубликована: Окт. 31, 2024

Язык: Английский

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An anoikis-related gene signature predicts prognosis, drug sensitivity, and immune microenvironment in cholangiocarcinoma

Heliyon, Год журнала: 2024, Номер 10(11), С. e32337 - e32337

Опубликована: Июнь 1, 2024

Язык: Английский

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