Peptide vaccination activating Galectin-3-specific T cells offers a novel means to target Galectin-3-expressing cells in the tumor microenvironment

Simone Kloch Bendtsen, Maria Perez-Penco, Mie Linder Hübbe, Evelina Martinenaite, Morten Orebo Holmström, Stine Emilie Weis-Banke, Nicolai Grønne Dahlager Jørgensen, Mia Aaboe Jørgensen, Shamaila Munir Ahmad, Kasper Mølgaard Jensen, Christina Friese, Mia Thorup Lundsager, Astrid Zedlitz Johansen, Marco Carretta, Niels Ødum, Özcan Met, Inge Marie Svane, Daniel Hargbøl Madsen, Mads Hald Andersen

Abstract

Galectin-3 (Gal3) can be expressed by many cells in the tumor microenvironment (TME), including cancer cells, cancer-associated fibroblasts, tumor-associated macrophages, and regulatory T cells (Tregs). In addition to immunosuppression, Gal3 expression has been connected to malignant cell transformation, tumor progression, and metastasis. In the present study, we found spontaneous T-cell responses against Gal3-derived peptides in PBMCs from both healthy donors and cancer patients. We isolated and expanded these Gal3-specific T cells in vitro and showed that they could directly recognize target cells that expressed Gal3. Finally, therapeutic vaccination with a long Gal3-derived peptide epitope, which induced the expansion of Gal3-specific CD8+ T cells in vivo, showed a significant tumor-growth delay in mice inoculated with EO771.LMB metastatic mammary tumor cells. This was associated with a significantly lower percentage of both Tregs and tumor-infiltrating Gal3+ cells in the non-myeloid CD45+CD11b- compartment and with an alteration of the T-cell memory populations in the spleens of Gal3-vaccinated mice. These results suggest that by activating Gal3-specific T cells by an immune-modulatory vaccination, we can target Gal3-producing cells in the TME, and thereby induce a more immune permissive TME. This indicates that Gal3 could be a novel target for therapeutic cancer vaccines.

OriginalsprogEngelsk
Artikelnummer2026020
TidsskriftOncoImmunology
Vol/bind11
Udgave nummer1
Sider (fra-til)2026020
ISSN2162-4011
DOI
StatusUdgivet - 27 jan. 2022

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