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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

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...

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Autores principales: Raineri, Davide, Cappellano, Giuseppe, Vilardo, Beatrice, Maione, Federica, Clemente, Nausicaa, Canciani, Elena, Boggio, Elena, Gigliotti, Casimiro Luca, Monge, Chiara, Dianzani, Chiara, Boldorini, Renzo, Dianzani, Umberto, Chiocchetti, Annalisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8772802/
https://www.ncbi.nlm.nih.gov/pubmed/35052731
http://dx.doi.org/10.3390/biomedicines10010051
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author Raineri, Davide
Cappellano, Giuseppe
Vilardo, Beatrice
Maione, Federica
Clemente, Nausicaa
Canciani, Elena
Boggio, Elena
Gigliotti, Casimiro Luca
Monge, Chiara
Dianzani, Chiara
Boldorini, Renzo
Dianzani, Umberto
Chiocchetti, Annalisa
author_facet Raineri, Davide
Cappellano, Giuseppe
Vilardo, Beatrice
Maione, Federica
Clemente, Nausicaa
Canciani, Elena
Boggio, Elena
Gigliotti, Casimiro Luca
Monge, Chiara
Dianzani, Chiara
Boldorini, Renzo
Dianzani, Umberto
Chiocchetti, Annalisa
author_sort Raineri, Davide
collection PubMed
description 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.
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spelling pubmed-87728022022-01-21 Inducible T-Cell Costimulator Ligand Plays a Dual Role in Melanoma Metastasis upon Binding to Osteopontin or Inducible T-Cell Costimulator Raineri, Davide Cappellano, Giuseppe Vilardo, Beatrice Maione, Federica Clemente, Nausicaa Canciani, Elena Boggio, Elena Gigliotti, Casimiro Luca Monge, Chiara Dianzani, Chiara Boldorini, Renzo Dianzani, Umberto Chiocchetti, Annalisa Biomedicines Article 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. MDPI 2021-12-27 /pmc/articles/PMC8772802/ /pubmed/35052731 http://dx.doi.org/10.3390/biomedicines10010051 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Raineri, Davide
Cappellano, Giuseppe
Vilardo, Beatrice
Maione, Federica
Clemente, Nausicaa
Canciani, Elena
Boggio, Elena
Gigliotti, Casimiro Luca
Monge, Chiara
Dianzani, Chiara
Boldorini, Renzo
Dianzani, Umberto
Chiocchetti, Annalisa
Inducible T-Cell Costimulator Ligand Plays a Dual Role in Melanoma Metastasis upon Binding to Osteopontin or Inducible T-Cell Costimulator
title Inducible T-Cell Costimulator Ligand Plays a Dual Role in Melanoma Metastasis upon Binding to Osteopontin or Inducible T-Cell Costimulator
title_full Inducible T-Cell Costimulator Ligand Plays a Dual Role in Melanoma Metastasis upon Binding to Osteopontin or Inducible T-Cell Costimulator
title_fullStr Inducible T-Cell Costimulator Ligand Plays a Dual Role in Melanoma Metastasis upon Binding to Osteopontin or Inducible T-Cell Costimulator
title_full_unstemmed Inducible T-Cell Costimulator Ligand Plays a Dual Role in Melanoma Metastasis upon Binding to Osteopontin or Inducible T-Cell Costimulator
title_short Inducible T-Cell Costimulator Ligand Plays a Dual Role in Melanoma Metastasis upon Binding to Osteopontin or Inducible T-Cell Costimulator
title_sort inducible t-cell costimulator ligand plays a dual role in melanoma metastasis upon binding to osteopontin or inducible t-cell costimulator
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8772802/
https://www.ncbi.nlm.nih.gov/pubmed/35052731
http://dx.doi.org/10.3390/biomedicines10010051
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