CTLA-4: Checkpoints beyond the membrane

Résumé fourni par la source

In 2018, the Nobel Prize in Physiology or Medicine was awarded to Professors James Allison and Tasuku Honjo for their pioneering research on CTLA-4 and PD-1. The discovery that the checkpoint receptors CTLA-4 and PD-1 regulate anti-tumor T cell immunity has revolutionized the field of cancer therapy since ipilimumab, a monoclonal antibody (mAb) specific for CTLA-4, was first shown to prolong survival in patients with difficult-to-treat metastatic melanoma over 10 years ago. While the assumption has been that CTLA-4-targeting mAbs target the membrane-bound form of CTLA-4, an understudied soluble form of CTLA-4 (sCTLA-4) has also been described. In this issue of Molecular Therapy, Kennedy et al. comprehensively demonstrate that sCTLA-4 alone confers a growth advantage to tumor cells, and importantly, a monoclonal antibody specific for sCTLA-4, and not membrane (m)CTLA-4, proved an effective therapeutic agent in vivo. 1 Kennedy P.T. Saulters E.L. Duckworth A.D. Lim Y.J. Woolley J.F. Slupsky J.R. Cragg M.S. Ward F.J. Dahal L.N. Soluble CTLA-4 attenuates T-cell activation and modulates anti-tumour immunity. Mol. Ther. 2024; 32https://doi.org/10.1016/j.ymthe.2023.11.028 Abstract Full Text Full Text PDF Scopus (1) Google Scholar The authors provide further insights into the cellular mechanisms by which sCTLA-4 and anti-sCTLA-4 alter the tumor microenvironment (TME). These findings challenge long-held assumptions about the mechanism(s) of action of anti-CTLA-4 mAbs and provide a basis for considering the clinical potential of sCTLA-4-targeting mAbs. Soluble CTLA-4 attenuates T cell activation and modulates anti-tumor immunityKennedy et al.Molecular TherapyDecember 4, 2023In BriefThe role of soluble CTLA-4 in the immune regulation of cancer is poorly understood. In this study, Kennedy et al. identify a novel checkpoint function of this isoform, revealing it to suppress anti-tumor immunity and leverage therapy through its blockade. Full-Text PDF Open Access

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.