Tertiary lymphoid structure signatures are associated with survival and immunotherapy response in muscle-invasive
Lin Zhou1, Bin Xu1, Yushan Liu1
1Department of Urology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract:
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.
Insights
Immunotherapy targeting the PD-1-PD-L1 pathway shows promise for advanced bladder cancer. Identifying tumors with tertiary lymphoid structures (TLSs) may predict better survival and response to PD1 blockade treatments.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Immunotherapy blocking the PD-1-PD-L1 pathway offers durable tumor control and long-term survival in advanced bladder cancers.
- Response to PD-1 blockade immunotherapy is limited to a subset of patients, necessitating predictive biomarkers.
Purpose of the Study:
- To establish an immune-based classification of muscle-invasive bladder cancers (MIBCs) using gene expression profiles.
- To investigate the role of tertiary lymphoid structures (TLSs) in predicting response to PD-1 blockade therapy across various cancer types.
Main Methods:
- Analyzed gene expression profiles from 1763 MIBCs and 11,835 solid tumors from The Cancer Genome Atlas (TCGA).
- Developed an immune-based classification identifying six distinct tumor microenvironment phenotypes.
- Assessed tertiary lymphoid structure (TLS) marker expression and correlated it with clinical outcomes and PD-1 blockade response.
Main Results:
- Identified six immune-based phenotypes in MIBCs, with Class F characterized by a strong TLS gene expression signature.
- Demonstrated significant heterogeneity in TLS abundance across and within human cancer types.
- The Class F group exhibited improved survival rates and a high response to PD-1 blockade therapy.
Conclusions:
- Confirmed distinct immune subtypes in MIBC patients.
- TLS signatures represent a potential biomarker for guiding clinical decision-making and treatment strategies for PD-1 blockade therapy.
