Peptide vaccination activating Galectin-3-specific T cells offers a novel means to target Galectin-3-expressing cells in the tumor microenvironment.
Peptide vaccination activating Galectin-3-specific T cells offers a novel means to target Galectin-3-expressing cells in the tumor microenvironment.
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DOI：
10.1080/2162402x.2022.2026020
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发表时间：
2022
期刊：
影响因子：
7.2
通讯作者：
Andersen MH
中科院分区：
文献类型：
--
作者：
Bendtsen SK;Perez-Penco M;Hübbe ML;Martinenaite E;Orebo Holmström M;Weis-Banke SE;Grønne Dahlager Jørgensen N;Jørgensen MA;Munir Ahmad S;Jensen KM;Friese C;Lundsager MT;Johansen AZ;Carretta M;Ødum N;Met Ö;Svane IM;Madsen DH;Andersen MH
Galectin-3(Galectin-3，Galectin-3)可由肿瘤微环境(TME)中的多种细胞表达，包括癌细胞、肿瘤相关成纤维细胞、肿瘤相关巨噬细胞和调节性T细胞(Treg)。除了免疫抑制，Gal3的表达还与恶性细胞转化、肿瘤进展和转移有关。在本研究中，我们在健康供者和癌症患者的PBMCs中发现了针对Gal3衍生多肽的自发T细胞反应。我们在体外分离和扩增了这些Gal3特异性T细胞，结果表明它们可以直接识别表达Gal3的靶细胞。最后，在体内诱导Gal3特异性CD8+T细胞扩增的Gal3衍生的长肽表位治疗性疫苗，在接种EO771的小鼠中显示出显著的肿瘤生长延迟。这与在非髓系CD45+CD11b−隔室中Treg细胞和肿瘤浸润性Gal3+细胞的百分比显著降低有关，并与Gal3免疫小鼠脾中T细胞记忆群体的改变有关。这些结果表明，通过免疫调节疫苗激活Gal3特异性T细胞，我们可以靶向TME中产生Gal3的细胞，从而诱导更多的免疫允许性TME。这表明Gal3可能成为治疗性肿瘤疫苗的新靶点。
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.
影响因子：
5.2
作者：
Wieërs G;Demotte N;Godelaine D;Van der Bruggen P
通讯作者：
Van der Bruggen P