TY - JOUR

T1 - Peptide vaccination activating Galectin-3-specific T cells offers a novel means to target Galectin-3-expressing cells in the tumor microenvironment

AU - Bendtsen, Simone Kloch

AU - Perez-Penco, Maria

AU - Hübbe, Mie Linder

AU - Martinenaite, Evelina

AU - Orebo Holmström, Morten

AU - Weis-Banke, Stine Emilie

AU - Grønne Dahlager Jørgensen, Nicolai

AU - Jørgensen, Mia Aaboe

AU - Munir Ahmad, Shamaila

AU - Jensen, Kasper Mølgaard

AU - Friese, Christina

AU - Lundsager, Mia Thorup

AU - Johansen, Astrid Zedlitz

AU - Carretta, Marco

AU - Ødum, Niels

AU - Met, Özcan

AU - Svane, Inge Marie

AU - Madsen, Daniel Hargbøl

AU - Andersen, Mads Hald

N1 - Publisher Copyright: © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - Gal3

KW - Galectin-3

KW - immune modulatory vaccine

KW - tumor microenvironment

U2 - 10.1080/2162402X.2022.2026020

DO - 10.1080/2162402X.2022.2026020

M3 - Journal article

C2 - 35111385

AN - SCOPUS:85123845092

VL - 11

JO - OncoImmunology

JF - OncoImmunology

SN - 2162-4011

IS - 1

M1 - 2026020

ER -