Anti-TIGIT antibody improves PD-L1 blockade through myeloid and T <subscript>reg</subscript> cells.
In: Nature, Jg. 627 (2024-03-01), Heft 8004, S. 646-655
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Zugriff:
Tiragolumab, an anti-TIGIT antibody with an active IgG1κ Fc, demonstrated improved outcomes in the phase 2 CITYSCAPE trial (ClinicalTrials.gov: NCT03563716 ) when combined with atezolizumab (anti-PD-L1) versus atezolizumab alone 1 . However, there remains little consensus on the mechanism(s) of response with this combination 2 . Here we find that a high baseline of intratumoural macrophages and regulatory T cells is associated with better outcomes in patients treated with atezolizumab plus tiragolumab but not with atezolizumab alone. Serum sample analysis revealed that macrophage activation is associated with a clinical benefit in patients who received the combination treatment. In mouse tumour models, tiragolumab surrogate antibodies inflamed tumour-associated macrophages, monocytes and dendritic cells through Fcγ receptors (FcγR), in turn driving anti-tumour CD8 + T cells from an exhausted effector-like state to a more memory-like state. These results reveal a mechanism of action through which TIGIT checkpoint inhibitors can remodel immunosuppressive tumour microenvironments, and suggest that FcγR engagement is an important consideration in anti-TIGIT antibody development.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Titel: |
Anti-TIGIT antibody improves PD-L1 blockade through myeloid and T <subscript>reg</subscript> cells.
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Autor/in / Beteiligte Person: | Guan, X ; Hu, R ; Choi, Y ; Srivats, S ; Nabet, BY ; Silva, J ; McGinnis, L ; Hendricks, R ; Nutsch, K ; Banta, KL ; Duong, E ; Dunkle, A ; Chang, PS ; Han, CJ ; Mittman, S ; Molden, N ; Daggumati, P ; Connolly, W ; Johnson, M ; Abreu, DR ; Cho, BC ; Italiano, A ; Gil-Bazo, I ; Felip, E ; Mellman, I ; Mariathasan, S ; Shames, DS ; Meng, R ; Chiang, EY ; Johnston, RJ ; Patil, NS |
Zeitschrift: | Nature, Jg. 627 (2024-03-01), Heft 8004, S. 646-655 |
Veröffentlichung: | Basingstoke : Nature Publishing Group ; <i>Original Publication</i>: London, Macmillan Journals ltd., 2024 |
Medientyp: | academicJournal |
ISSN: | 1476-4687 (electronic) |
DOI: | 10.1038/s41586-024-07121-9 |
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