TY - JOUR
T1 - Vaccination against galectin-1 promotes cytotoxic T-cell infiltration in melanoma and reduces tumor burden
AU - Femel, Julia
AU - van Hooren, Luuk
AU - Herre, Melanie
AU - Cedervall, Jessica
AU - Saupe, Falk
AU - Huijbers, Elisabeth J. M.
AU - Verboogen, Danielle R. J.
AU - Reichel, Matthias
AU - Thijssen, Victor L.
AU - Griffioen, Arjan W.
AU - Hellman, Lars
AU - Dimberg, Anna
AU - Olsson, Anna-Karin
N1 - Funding Information: This work was supported by grants to AKO from The Swedish Research Council (Medicine and Health) #2010-6903-75363-44 and The Swedish Cancer Society #11 0653. The authors declare no potential conflicts of interest. Publisher Copyright: © 2022, The Author(s).
PY - 2022/8
Y1 - 2022/8
N2 - 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.
AB - 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.
KW - Cancer vaccine
KW - Galectin-1
KW - Granzyme B
KW - Immunization
KW - T cells
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85122734498&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/35018481
U2 - https://doi.org/10.1007/s00262-021-03139-4
DO - https://doi.org/10.1007/s00262-021-03139-4
M3 - Article
C2 - 35018481
SN - 0340-7004
VL - 71
SP - 2029
EP - 2040
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
IS - 8
ER -