TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells.

ABSTRACT: Therapeutic antibodies that block the programmed death-1 (PD-1)-programmed death-ligand 1 (PD-L1) pathway can induce robust and durable responses in patients with various cancers, including metastatic urothelial cancer. However, these responses only occur in a subset of patients. Elucidating the determinants of response and resistance is key to improving outcomes and developing new treatment strategies. Here we examined tumours from a large cohort of patients with metastatic urothelial cancer who were treated with an anti-PD-L1 agent (atezolizumab) and identified major determinants of clinical outcome. Response to treatment was associated with CD8⁺ T-effector cell phenotype and, to an even greater extent, high neoantigen or tumour mutation burden. Lack of response was associated

SUBMITTER: Mariathasan S 

PROVIDER: S-EPMC6028240 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature