RESUMEN
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.
Asunto(s)
Vacunas contra el Cáncer , Neoplasias , Animales , Linfocitos T CD8-positivos/metabolismo , Galectina 3/metabolismo , Humanos , Ratones , Microambiente Tumoral , Vacunación , Vacunas de SubunidadRESUMEN
Adoptive cell therapy (ACT) utilizing either tumor-infiltrating lymphocyte (TIL)-derived T cells or T cells genetically engineered to express tumor recognizing receptors has emerged as a powerful and potentially curative therapy for several cancers. Many ACT-based therapies have recently entered late-phase clinical testing, with several T cell therapies already achieving regulatory approval for the treatment of patients with B cell malignancies. In this review, we briefly outline the principles of adoptively transferred T cells for the treatment of cancer.