Loss of two-pore channel 2 enhances CD8+ T cell cytotoxicity and directly impairs tumour growth via MAPK axis in HCC
Our findings identify TPC2 as a dual regulator of tumour-intrinsic signalling and immune evasion in HCC. By modulating oncogenic MAPK activity and antigen presentation pathways, TPC2 influences both cancer progression and responsiveness to immunotherapy. Targeting TPC2 therefore represents a promising strategy to enhance immune checkpoint inhibitor efficacy in hepatocellular carcinoma.
Authors
- Stefania Forciniti (ORCID: https://orcid.org/0000-0001-6719-1591)
- Salvatore Nigro (ORCID: https://orcid.org/0000-0001-7566-7983)
- Thomas Fröhlich (ORCID: https://orcid.org/0000-0002-4709-3211)
- Christian Grimm (ORCID: https://orcid.org/0000-0002-0177-5559)
- Dana Matzek
- Bastian Popper (ORCID: https://orcid.org/0000-0003-1517-695X)
- Olivia M. Merkel (ORCID: https://orcid.org/0000-0002-4151-3916)
- Valentina Onesto (ORCID: https://orcid.org/0000-0002-2308-4126)
- Karin Bartel (ORCID: https://orcid.org/0000-0002-6634-547X)
- Carla Abrahamian (ORCID: https://orcid.org/0000-0002-0425-8004)
- Giuseppe Gigli (ORCID: https://orcid.org/0000-0002-2583-5747)
- Helena Iuele (ORCID: https://orcid.org/0000-0002-9188-0511)
- Sebastian Theurich (ORCID: https://orcid.org/0000-0001-5706-8258)
- Amar Hadzic
- André Kübler
- Jan B. Stöckl (ORCID: https://orcid.org/0000-0002-6432-1271)
- Loretta L. del Mercato (ORCID: https://orcid.org/0000-0001-9733-7088)
- Lina Ouologuem (ORCID: https://orcid.org/0009-0007-4648-3641)
- Anna Chiara Siciliano (ORCID: https://orcid.org/0009-0004-7636-4705)
- Anny Nguyen
- Sarah Ouologuem
Institutions
- German Cancer Research Center (DE)
- Heidelberg University (DE)
- University of Oxford (GB)
- Istituto di Nanotecnologia (IT)
- Fraunhofer Institute for Translational Medicine and Pharmacology (DE)
- Munich Cluster for Systems Neurology (DE)
- German Centre for Cardiovascular Research (DE)
- Science Oxford (GB)
- Deutsches Herzzentrum München (DE)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Frontiers in Immunology
- Published
- 2025-10-24
- DOI
- https://doi.org/10.3389/fimmu.2025.1668066
- Primary Topic
- Adenosine and Purinergic Signaling
- Type
- article
- Field-Weighted Citation Impact
- 0.00