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Anti-TIGIT antibody improves PD-L1 blockade through myeloid and Treg cells

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 ....

South Korea , Cytometryb Clin , Laboratory For Functional Epigenetics , Cancer Biol , Cancer Ther , Molecular Signatures Database , Proteome Res , Acids Res , Functional Epigenetics ,

Type 1 diabetes

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. ....

United Kingdom , Nordrhein Westfalen , Sri Lanka , Southern Ostrobothnia , United States , North Yorkshire , Cardiovasc Diabetol , Pediatr Nephrol , J Clin Endocrinol , Nat Genet , Hosseini Fard , Al Taji , Adolesc Nutr , American Diabetes Association Professional Pratice Committee , American Diabetes Association Professional Practice Committee , Market Research , Id Exchange , Health Promot Perspect , National Youth Tobacco , Steno Diabetes Center Copenhagen , Endocrine Society , European Association For The Study Of Diabetes , International Diabetes Federation Atlas , Diabetes Study Group , Lancet Child Adolesc Health , American Diabetes Association ,

The role of autoantibodies biomarkers in precision medicine

This article outlines the powerful role of biomarkers in precision medicine, such as the use of autoantibodies for drug discovery against cancer. ....

United States , Nat Genet , Gama Duarte , Van Norman , Maria Osipova , Clin Rheumatol , Klunket Al , Van Regenmortel , High Mobility Group Nucleosome Binding Domain , National Cancer Institute , Sponsored Content , Humoral Immune , Testis Antigen , Testis Specific Proteiny Linked , Cancer Testis Antigen , Mobility Group Nucleosome Binding Domain , Zipper Protein , Monophosphate Dehydrogenase , Fused Gene , Serine Threonine Protein Phosphatase , Cancer Testis , Tumor Markers , Bacillus Calmette Guerin , Ome Microarray , Image Credit , Proteome Res ,