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The immunomodulatory molecule TIGIT is expressed by chronic lymphocytic leukemia cells and contributes to anergy

T-cell immunoreceptor with Ig and ITIM domains (TIGIT) is an inhibitory checkpoint receptor that negatively regulates T-cell responses. CD226 competes with TIGIT for binding to the CD155 ligand, delivering a positive signal to the T cell. Here we studied the expression of TIGIT and CD226 in a cohort...

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Autores principales: Arruga, Francesca, Rubin, Marta, Papazoglou, Despoina, Iannello, Andrea, Ioannou, Nikolaos, Moia, Riccardo, Rossi, Davide, Gaidano, Gianluca, Coscia, Marta, Laurenti, Luca, D’Arena, Giovanni, Allan, John N., Furman, Richard R., Vaisitti, Tiziana, Ramsay, Alan G., Deaglio, Silvia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Fondazione Ferrata Storti 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10388274/
https://www.ncbi.nlm.nih.gov/pubmed/36655432
http://dx.doi.org/10.3324/haematol.2022.282177
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author Arruga, Francesca
Rubin, Marta
Papazoglou, Despoina
Iannello, Andrea
Ioannou, Nikolaos
Moia, Riccardo
Rossi, Davide
Gaidano, Gianluca
Coscia, Marta
Laurenti, Luca
D’Arena, Giovanni
Allan, John N.
Furman, Richard R.
Vaisitti, Tiziana
Ramsay, Alan G.
Deaglio, Silvia
author_facet Arruga, Francesca
Rubin, Marta
Papazoglou, Despoina
Iannello, Andrea
Ioannou, Nikolaos
Moia, Riccardo
Rossi, Davide
Gaidano, Gianluca
Coscia, Marta
Laurenti, Luca
D’Arena, Giovanni
Allan, John N.
Furman, Richard R.
Vaisitti, Tiziana
Ramsay, Alan G.
Deaglio, Silvia
author_sort Arruga, Francesca
collection PubMed
description T-cell immunoreceptor with Ig and ITIM domains (TIGIT) is an inhibitory checkpoint receptor that negatively regulates T-cell responses. CD226 competes with TIGIT for binding to the CD155 ligand, delivering a positive signal to the T cell. Here we studied the expression of TIGIT and CD226 in a cohort of 115 patients with chronic lymphocytic leukemia (CLL) and report expression of TIGIT and CD226 by leukemic cells. By devising a TIGIT/CD226 ratio, we showed that CLL cells favoring TIGIT over CD226 are typical of a more indolent disease, while those favoring CD226 are characterized by a shorter time to first treatment and shorter progression-free survival after first treatment. TIGIT expression was inversely correlated to the B-cell receptor (BCR) signaling capacity, as determined by studying BTK phosphorylation, cell proliferation and interleukin-10 production. In CLL cells treated with ibrutinib, in which surface IgM and BCR signaling capacity are temporarily increased, TIGIT expression was downmodulated, in line with data indicating transient recovery from anergy. Lastly, cells from patients with Richter syndrome were characterized by high levels of CD226, with low to undetectable TIGIT, in keeping with their high proliferative drive. Together, these data suggest that TIGIT contributes to CLL anergy by down-regulating BCR signaling, identifying novel and actionable molecular circuits regulating anergy and modulating CLL cell functions.
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spelling pubmed-103882742023-08-01 The immunomodulatory molecule TIGIT is expressed by chronic lymphocytic leukemia cells and contributes to anergy Arruga, Francesca Rubin, Marta Papazoglou, Despoina Iannello, Andrea Ioannou, Nikolaos Moia, Riccardo Rossi, Davide Gaidano, Gianluca Coscia, Marta Laurenti, Luca D’Arena, Giovanni Allan, John N. Furman, Richard R. Vaisitti, Tiziana Ramsay, Alan G. Deaglio, Silvia Haematologica Article - Chronic Lymphocytic Leukemia T-cell immunoreceptor with Ig and ITIM domains (TIGIT) is an inhibitory checkpoint receptor that negatively regulates T-cell responses. CD226 competes with TIGIT for binding to the CD155 ligand, delivering a positive signal to the T cell. Here we studied the expression of TIGIT and CD226 in a cohort of 115 patients with chronic lymphocytic leukemia (CLL) and report expression of TIGIT and CD226 by leukemic cells. By devising a TIGIT/CD226 ratio, we showed that CLL cells favoring TIGIT over CD226 are typical of a more indolent disease, while those favoring CD226 are characterized by a shorter time to first treatment and shorter progression-free survival after first treatment. TIGIT expression was inversely correlated to the B-cell receptor (BCR) signaling capacity, as determined by studying BTK phosphorylation, cell proliferation and interleukin-10 production. In CLL cells treated with ibrutinib, in which surface IgM and BCR signaling capacity are temporarily increased, TIGIT expression was downmodulated, in line with data indicating transient recovery from anergy. Lastly, cells from patients with Richter syndrome were characterized by high levels of CD226, with low to undetectable TIGIT, in keeping with their high proliferative drive. Together, these data suggest that TIGIT contributes to CLL anergy by down-regulating BCR signaling, identifying novel and actionable molecular circuits regulating anergy and modulating CLL cell functions. Fondazione Ferrata Storti 2023-01-19 /pmc/articles/PMC10388274/ /pubmed/36655432 http://dx.doi.org/10.3324/haematol.2022.282177 Text en Copyright© 2023 Ferrata Storti Foundation https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution Noncommercial License (by-nc 4.0) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Article - Chronic Lymphocytic Leukemia
Arruga, Francesca
Rubin, Marta
Papazoglou, Despoina
Iannello, Andrea
Ioannou, Nikolaos
Moia, Riccardo
Rossi, Davide
Gaidano, Gianluca
Coscia, Marta
Laurenti, Luca
D’Arena, Giovanni
Allan, John N.
Furman, Richard R.
Vaisitti, Tiziana
Ramsay, Alan G.
Deaglio, Silvia
The immunomodulatory molecule TIGIT is expressed by chronic lymphocytic leukemia cells and contributes to anergy
title The immunomodulatory molecule TIGIT is expressed by chronic lymphocytic leukemia cells and contributes to anergy
title_full The immunomodulatory molecule TIGIT is expressed by chronic lymphocytic leukemia cells and contributes to anergy
title_fullStr The immunomodulatory molecule TIGIT is expressed by chronic lymphocytic leukemia cells and contributes to anergy
title_full_unstemmed The immunomodulatory molecule TIGIT is expressed by chronic lymphocytic leukemia cells and contributes to anergy
title_short The immunomodulatory molecule TIGIT is expressed by chronic lymphocytic leukemia cells and contributes to anergy
title_sort immunomodulatory molecule tigit is expressed by chronic lymphocytic leukemia cells and contributes to anergy
topic Article - Chronic Lymphocytic Leukemia
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10388274/
https://www.ncbi.nlm.nih.gov/pubmed/36655432
http://dx.doi.org/10.3324/haematol.2022.282177
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