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
Type 1 diabetes is a chronic disease caused by autoimmune destruction of pancreatic
β cells. Individuals with type 1 diabetes are reliant on insulin for survival. Despite
enhanced knowledge related to the pathophysiology of the disease, including interactions
between genetic, immune, and environmental contributions, and major strides in treatment
and management, disease burden remains high. Studies aimed at blocking the immune
attack on β cells in people at risk or individuals with very early onset type 1 diabetes
show promise in preserving endogenous insulin production.