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REVIEW article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1495907
This article is part of the Research Topic Community Series in Beyond PD-1: Novel Checkpoint Receptors and Ligands as Targets for Immunotherapy, Volume II View all articles

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

Provisionally accepted
Christin Knickmeier Christin Knickmeier 1Gaetan Aime Noubissi Nzeteu Gaetan Aime Noubissi Nzeteu 1Bernhard F Gibbs Bernhard F Gibbs 2Frederik J Hoogwater Frederik J Hoogwater 3Maarten W Nijkamp Maarten W Nijkamp 3Maximilian Bockhorn Maximilian Bockhorn 1,4N. Helge Meyer N. Helge Meyer 1*
  • 1 University of Oldenburg, Oldenburg, Germany
  • 2 Canterbury Christ Church University, Canterbury, United Kingdom
  • 3 University Medical Center Groningen, Groningen, Netherlands, Netherlands
  • 4 Klinikum Oldenburg, Oldenburg, Lower Saxony, Germany

The final, formatted version of the article will be published soon.

    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.

    Keywords: Pancreatic Ductal Adenocarcinoma, Tumor immune microenvironment, Immunotherapy, immune checkpoints, galectin-9, myeloid-derived suppressor cells, macrophage (re-)polarization

    Received: 13 Sep 2024; Accepted: 13 Jan 2025.

    Copyright: © 2025 Knickmeier, Noubissi Nzeteu, Gibbs, Hoogwater, Nijkamp, Bockhorn and Meyer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: N. Helge Meyer, University of Oldenburg, Oldenburg, Germany

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.