학술논문
Anti-TIGIT antibody improves PD-L1 blockade through myeloid and Treg cells
Document Type
Original Paper
Author
Guan, Xiangnan; Hu, Ruozhen; Choi, Yoonha; Srivats, Shyam; Nabet, Barzin Y.; Silva, John; McGinnis, Lisa; Hendricks, Robert; Nutsch, Katherine; Banta, Karl L.; Duong, Ellen; Dunkle, Alexis; Chang, Patrick S.; Han, Chia-Jung; Mittman, Stephanie; Molden, Nandini; Daggumati, Pallavi; Connolly, Wendy; Johnson, Melissa; Abreu, Delvys Rodriguez; Cho, Byoung Chul; Italiano, Antoine; Gil-Bazo, Ignacio; Felip, Enriqueta; Mellman, Ira; Mariathasan, Sanjeev; Shames, David S.; Meng, Raymond; Chiang, Eugene Y.; Johnston, Robert J.; Patil, Namrata S.
Source
Nature: International weekly journal of science. 627(8004):646-655
Subject
Language
English
ISSN
0028-0836
1476-4687
1476-4687
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.
A high baseline of intratumoural macrophages and regulatory T cells is associated with better outcomes in patients with non-small cell lung cancer treated with atezolizumab plus tiragolumab, but not with atezolizumab alone.
A high baseline of intratumoural macrophages and regulatory T cells is associated with better outcomes in patients with non-small cell lung cancer treated with atezolizumab plus tiragolumab, but not with atezolizumab alone.