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Inducible T-Cell Costimulator Ligand Plays a Dual Role in Melanoma Metastasis upon Binding to Osteopontin or Inducible T-Cell Costimulator

Authors :
Davide Raineri
Giuseppe Cappellano
Beatrice Vilardo
Federica Maione
Nausicaa Clemente
Elena Canciani
Elena Boggio
Casimiro Luca Gigliotti
Chiara Monge
Chiara Dianzani
Renzo Boldorini
Umberto Dianzani
Annalisa Chiocchetti
Source :
Biomedicines, Vol 10, Iss 51, p 51 (2022), Biomedicines, Biomedicines; Volume 10; Issue 1; Pages: 51
Publication Year :
2021
Publisher :
Zenodo, 2021.

Abstract

Recently, we demonstrated that inducible T-cell costimulator (ICOS) shares its unique ligand (ICOSL) with osteopontin (OPN), and OPN/ICOSL binding promotes tumor metastasis and angiogenesis in the 4T1 breast cancer model. Literature showed that OPN promotes melanoma metastasis by suppressing T-cell activation and recruiting myeloid suppressor cells (MDSC). On the opposite, ICOS/ICOSL interaction usually sustains an antitumor response. Here, we engineered murine B16F10 melanoma cells, by transfecting or silencing ICOSL. In vitro data showed that loss of ICOSL favors anchorage-independent growth and induces more metastases in vivo, compared to ICOSL expressing cells. To dissect individual roles of the three molecules, we compared data from C57BL/6 with those from OPN-KO, ICOS-KO, and ICOSL-KO mice, missing one partner at a time. We found that OPN produced by the tumor microenvironment (TME) favors the metastasis by interacting with stromal ICOSL. This activity is dominantly inhibited by ICOS expressed on TME by promoting Treg expansion. Importantly, we also show that OPN and ICOSL highly interact in human melanoma metastases compared to primary tumors. Interfering with this binding may be explored in immunotherapy either for nonresponding or patients resistant to conventional therapies.

Details

Language :
English
Database :
OpenAIRE
Journal :
Biomedicines, Vol 10, Iss 51, p 51 (2022), Biomedicines, Biomedicines; Volume 10; Issue 1; Pages: 51
Accession number :
edsair.doi.dedup.....2a4923b81b556cab7ed2d0a53a23d4c8
Full Text :
https://doi.org/10.5281/zenodo.6576607