It’s about TIME – Gal-9 as a potential immunotherapeutic target in pancreatic ductal adenocarcinoma
Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, characterized by an extremely poor prognosis and limited therapeutic options. Central to the progression and immune evasion of PDAC is the tumor (immune) microenvironment (TIME), where immune checkpoint proteins suc...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1495907/full |
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| author | Christin Knickmeier Gaetan Aime Noubissi Nzeteu Bernhard F. Gibbs Frederik J. H. Hoogwater Maarten W. Nijkamp Maximilian Bockhorn N. Helge Meyer |
| author_facet | Christin Knickmeier Gaetan Aime Noubissi Nzeteu Bernhard F. Gibbs Frederik J. H. Hoogwater Maarten W. Nijkamp Maximilian Bockhorn N. Helge Meyer |
| author_sort | Christin Knickmeier |
| collection | DOAJ |
| description | Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, characterized by an extremely poor prognosis and limited therapeutic options. Central to the progression and immune evasion of PDAC is the tumor (immune) microenvironment (TIME), where immune checkpoint proteins such as galectin-9 (Gal-9) play pivotal roles. Gal-9 significantly contributes to the immunosuppressive milieu of PDAC by interacting with various immune cells, such as T cells, macrophages, and myeloid-derived suppressor cells (MDSCs). These interactions suppress anti-tumor immunity, thus facilitating tumor growth and metastasis. This review comprehensively examines the multifaceted role of Gal-9 in the TIME of PDAC, detailing its mechanisms of action, including the induction of regulatory T cells, polarization of tumor-associated macrophages, and modulation of apoptotic pathways via Tim-3 and caspase activation. The therapeutic potential of targeting Gal-9, either alone or in combination with other immune checkpoint inhibitors such as anti-PD-L1, is also discussed, highlighting preclinical findings that suggest promising avenues for enhancing anti-tumor immune responses. By elucidating the complex biological activities of Gal-9 and its interactions within the TIME, this review underscores the importance of innovative therapeutic strategies aimed at mitigating the immunosuppressive effects of Gal-9 in PDAC. |
| format | Article |
| id | doaj-art-b9ddb52a654b40208f9c260b0e7e3238 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-b9ddb52a654b40208f9c260b0e7e32382025-01-31T06:40:17ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.14959071495907It’s about TIME – Gal-9 as a potential immunotherapeutic target in pancreatic ductal adenocarcinomaChristin Knickmeier0Gaetan Aime Noubissi Nzeteu1Bernhard F. Gibbs2Frederik J. H. Hoogwater3Maarten W. Nijkamp4Maximilian Bockhorn5N. Helge Meyer6Department of Human Medicine, School of Medicine and Health Sciences, Carl von Ossietzky Universität Oldenburg and University Hospital for General and Visceral Surgery, Oldenburg, GermanyDepartment of Human Medicine, School of Medicine and Health Sciences, Carl von Ossietzky Universität Oldenburg and University Hospital for General and Visceral Surgery, Oldenburg, GermanySchool of Psychology and Life Sciences, Canterbury Christ Church University, Canterbury, United KingdomSection of HPB Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsSection of HPB Surgery and Liver Transplantation, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, NetherlandsDepartment of Human Medicine, School of Medicine and Health Sciences, Carl von Ossietzky Universität Oldenburg and University Hospital for General and Visceral Surgery, Oldenburg, GermanyDepartment of Human Medicine, School of Medicine and Health Sciences, Carl von Ossietzky Universität Oldenburg and University Hospital for General and Visceral Surgery, Oldenburg, GermanyPancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, characterized by an extremely poor prognosis and limited therapeutic options. Central to the progression and immune evasion of PDAC is the tumor (immune) microenvironment (TIME), where immune checkpoint proteins such as galectin-9 (Gal-9) play pivotal roles. Gal-9 significantly contributes to the immunosuppressive milieu of PDAC by interacting with various immune cells, such as T cells, macrophages, and myeloid-derived suppressor cells (MDSCs). These interactions suppress anti-tumor immunity, thus facilitating tumor growth and metastasis. This review comprehensively examines the multifaceted role of Gal-9 in the TIME of PDAC, detailing its mechanisms of action, including the induction of regulatory T cells, polarization of tumor-associated macrophages, and modulation of apoptotic pathways via Tim-3 and caspase activation. The therapeutic potential of targeting Gal-9, either alone or in combination with other immune checkpoint inhibitors such as anti-PD-L1, is also discussed, highlighting preclinical findings that suggest promising avenues for enhancing anti-tumor immune responses. By elucidating the complex biological activities of Gal-9 and its interactions within the TIME, this review underscores the importance of innovative therapeutic strategies aimed at mitigating the immunosuppressive effects of Gal-9 in PDAC.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1495907/fullpancreatic ductal adenocarcinomatumor immune microenvironmentimmunotherapyimmune checkpointsgalectin-9myeloid-derived suppressor cells |
| spellingShingle | Christin Knickmeier Gaetan Aime Noubissi Nzeteu Bernhard F. Gibbs Frederik J. H. Hoogwater Maarten W. Nijkamp Maximilian Bockhorn N. Helge Meyer It’s about TIME – Gal-9 as a potential immunotherapeutic target in pancreatic ductal adenocarcinoma Frontiers in Immunology pancreatic ductal adenocarcinoma tumor immune microenvironment immunotherapy immune checkpoints galectin-9 myeloid-derived suppressor cells |
| title | It’s about TIME – Gal-9 as a potential immunotherapeutic target in pancreatic ductal adenocarcinoma |
| title_full | It’s about TIME – Gal-9 as a potential immunotherapeutic target in pancreatic ductal adenocarcinoma |
| title_fullStr | It’s about TIME – Gal-9 as a potential immunotherapeutic target in pancreatic ductal adenocarcinoma |
| title_full_unstemmed | It’s about TIME – Gal-9 as a potential immunotherapeutic target in pancreatic ductal adenocarcinoma |
| title_short | It’s about TIME – Gal-9 as a potential immunotherapeutic target in pancreatic ductal adenocarcinoma |
| title_sort | it s about time gal 9 as a potential immunotherapeutic target in pancreatic ductal adenocarcinoma |
| topic | pancreatic ductal adenocarcinoma tumor immune microenvironment immunotherapy immune checkpoints galectin-9 myeloid-derived suppressor cells |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1495907/full |
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