학술논문
Vaccination against galectin-1 promotes cytotoxic T-cell infiltration in melanoma and reduces tumor burden.
Document Type
Academic Journal
Author
Femel J; Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Biomedical Center, Box 582, 75123, Uppsala, Sweden.; van Hooren L; Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 75185, Uppsala, Sweden.; Division of Tumor Biology and Immunology, Netherlands Cancer Institute, Oncode Institute, Box 596, 1066CX, Amsterdam, The Netherlands.; Herre M; Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Biomedical Center, Box 582, 75123, Uppsala, Sweden.; Cedervall J; Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Biomedical Center, Box 582, 75123, Uppsala, Sweden.; Saupe F; Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Biomedical Center, Box 582, 75123, Uppsala, Sweden.; Huijbers EJM; Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Biomedical Center, Box 582, 75123, Uppsala, Sweden.; Angiogenesis Laboratory, Department of Medical Oncology, Cancer Center Amsterdam (CCA), Amsterdam UMC, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.; Verboogen DRJ; Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Biomedical Center, Box 582, 75123, Uppsala, Sweden.; Reichel M; Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Biomedical Center, Box 582, 75123, Uppsala, Sweden.; Thijssen VL; Department of Radiation Oncology, Amsterdam UMC, Amsterdam, The Netherlands.; Griffioen AW; Angiogenesis Laboratory, Department of Medical Oncology, Cancer Center Amsterdam (CCA), Amsterdam UMC, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.; Hellman L; Department of Cell and Molecular Biology, Uppsala University, Biomedical Center, Box 596, 75124, Uppsala, Sweden.; Dimberg A; Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, 75185, Uppsala, Sweden.; Olsson AK; Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Biomedical Center, Box 582, 75123, Uppsala, Sweden. anna-karin.olsson@imbim.uu.se.
Source
Publisher: Springer Verlag Country of Publication: Germany NLM ID: 8605732 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0851 (Electronic) Linking ISSN: 03407004 NLM ISO Abbreviation: Cancer Immunol Immunother Subsets: MEDLINE
Subject
Language
English
Abstract
Galectin-1 (Gal1) is a glycan-binding protein that promotes tumor progression by several distinct mechanisms. Through direct binding to vascular endothelial growth factor (VEGF)-receptor 2, Gal1 is able to induce VEGF-like signaling, which contributes to tumor angiogenesis. Furthermore, several studies have demonstrated an immunosuppressive function of Gal1 through effects on both effector and regulatory T cells. Elevated Gal1 expression and secretion have been shown in many tumor types, and high Gal1 serum levels have been connected to poor prognosis in cancer patients. These findings suggest that therapeutic strategies directed against Gal1 would enable simultaneous targeting of angiogenesis, immune evasion and metastasis. In the current study, we have analyzed the potential of Gal1 as a cancer vaccine target. We show that it is possible to generate high anti-Gal1 antibody levels in mice immunized with a recombinant vaccine protein consisting of bacterial sequences fused to Gal1. Growth of Gal1 expressing melanomas was significantly impaired in the immunized mice compared to the control group. This was associated with improved perfusion of the tumor vasculature, as well as increased infiltration of macrophages and cytotoxic T cells (CTLs). The level of granzyme B, mainly originating from CTLs in our model, was significantly elevated in Gal1 vaccinated mice and correlated with a decrease in tumor burden. We conclude that vaccination against Gal1 is a promising pro-immunogenic approach for cancer therapy that could potentially enhance the effect of other immunotherapeutic strategies due to its ability to promote CTL influx in tumors.
(© 2022. The Author(s).)
(© 2022. The Author(s).)