Anti-TIGIT antibody improves PD-L1 blockade through myeloid and Treg cells.
Nature
; 627(8004): 646-655, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38418879
ABSTRACT
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 alone1. However, there remains little consensus on the mechanism(s) of response with this combination2. 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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Receptores Imunológicos
/
Linfócitos T Reguladores
/
Células Mieloides
/
Antígeno B7-H1
/
Anticorpos Monoclonais
/
Neoplasias
/
Antineoplásicos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Nature
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos