| First Author | Guan X | Year | 2024 |
| Journal | Nature | Volume | 627 |
| Issue | 8004 | Pages | 646-655 |
| PubMed ID | 38418879 | Mgi Jnum | J:352005 |
| Mgi Id | MGI:7660411 | Doi | 10.1038/s41586-024-07121-9 |
| Citation | Guan X, et al. (2024) Anti-TIGIT antibody improves PD-L1 blockade through myeloid and T(reg) cells. Nature 627(8004):646-655 |
| abstractText | Tiragolumab, an anti-TIGIT antibody with an active IgG1kappa 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 Fcgamma receptors (FcgammaR), 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 FcgammaR engagement is an important consideration in anti-TIGIT antibody development. |
