Inducible T-cell co-stimulator (ICOS) and ICOS ligand are novel players in the multiple-myeloma microenvironment.

Abstract

The inducible T-cell co-stimulator (ICOS) is a T-cell receptor that, once bound to ICOS ligand (ICOSL) expressed on several cell types including the B-cell lineage, plays a decisive role in adaptive immunity by regulating the interplay between B and T cells. In addition to its immunomodulatory functions, we have shown that ICOS/ICOSL signalling can inhibit the activity of osteoclasts, unveiling a novel mechanism of lymphocyte-bone cells interactions. ICOS and ICOSL can also be found as soluble forms, namely sICOS and sICOSL. Here we show that: (i) levels of sICOS and sICOSL are increased in multiple myeloma (MM) compared to monoclonal gammopathy of undetermined significance and smouldering MM; (ii) levels of sICOS and sICOSL variably correlate with several markers of tumour burden; and (iii) sICOS levels tend to be higher in Durie-Salmon stage II/III versus stage I MM and correlate with overall survival as an independent variable. Moreover, surface ICOS and ICOSL are expressed in both myeloma cells and normal plasma cells, where they probably regulate different functional stages. Finally, ICOSL triggering inhibits the migration of myeloma cell lines in vitro and the growth of ICOSL+ MOPC-21 myeloma cells in vivo. These results suggest that ICOS and ICOSL represent novel markers and therapeutic targets for MM.

• Authors: Elena Boggio, Casimiro Luca Gigliotti, Riccardo Moia, Annamaria Scotta, Ilaria Crespi, Paola Boggione, Lorenzo De Paoli, Clara Deambrogi, Massimiliano Garzaro, Matteo Vidali, Annalisa Chiocchetti, Ian Stoppa, Roberta Rolla, Chiara Dianzani, Chiara Monge, Nausicaa Clemente, Gianluca Gaidano, Umberto Dianzani
• Journal: British journal of haematology (Br J Haematol) Vol. 196 Issue 6 Pg. 1369-1380 (03 2022) ISSN: 1365-2141 [Electronic] England
• PMID: 34954822 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 British Society for Haematology and John Wiley & Sons Ltd.

Chemical References

• ICOS protein, human
• Inducible T-Cell Co-Stimulator Ligand
• Inducible T-Cell Co-Stimulator Protein
• Ligands

Topics

• Humans
• Inducible T-Cell Co-Stimulator Ligand (metabolism)
• Inducible T-Cell Co-Stimulator Protein (metabolism)
• Ligands
• Multiple Myeloma (metabolism)
• T-Lymphocytes
• Tumor Microenvironment