Tertiary lymphoid structure signatures are associated with survival and immunotherapy response in muscle-invasive bladder cancer

Immunotherapy that block PD-1–PD-L1 pathway can induce durable tumor control and result in the long-term survival of patients with advanced bladder cancers. However, these responses only occur in a subset of patients. We study gene expression profiles in 1763 muscle-invasive bladder cancers (MIBCs) and 11,835 solid tumors from TCGA. We establish an immune-based classification on the basis of the composition of the tumor microenvironment and identify six distinct phenotypes. The class F was characterized by a strong tertiary lymphoid structures (TLSs) related gene expression signature. Pan-cancer gene expression analysis of tertiary lymphoid structure markers in 11,835 solid tumors from TCGA unveiled the heterogeneity of TLSs abundance both within and between human cancer types. The class F group demonstrated improved survival and a high response rate to PD1 blockade. This work confirms the immune subtypes in patients with MIBC, and unravels the potential of TLS signatures to guide clinical decision-making and treatments.