Publications by authors named "Daniel H Shu"
Tertiary lymphoid structures (TLS) are organized collections of B and T lymphocytes that arise in nonlymphoid tissue in response to chronic, unresolved inflammation. TLS have structural and functional similarities to germinal centers found in lymph nodes and are believed to support the establishment of lymph node-like adaptive immune responses at local sites of inflammation. However, understanding of the underlying biology of these structures remains limited, particularly the different stages of TLS life cycle and the signals governing the initiation, maturation, and termination of TLS.
View Article and Find Full Text PDFTertiary lymphoid structures (TLS) are associated with improved response in solid tumors treated with immune checkpoint blockade, but understanding of the prognostic and predictive value of TLS and the circumstances of their resolution is incomplete. Here we show that in hepatocellular carcinoma treated with neoadjuvant immunotherapy, high intratumoral TLS density at the time of surgery is associated with pathologic response and improved relapse-free survival. In areas of tumor regression, we identify a noncanonical involuted morphology of TLS marked by dispersion of the B cell follicle, persistence of a T cell zone enriched for T cell-mature dendritic cell interactions and increased expression of T cell memory markers.
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- Researchers studied how immune checkpoint inhibitors (ICIs) used before liver surgery can affect tumor regression in patients with hepatocellular carcinoma and their impact on relapse-free survival.* -
- The analysis involved data from five clinical trials across various countries, focusing on adults with diagnosed liver cancer who had specific health criteria and no previous ICI treatments.* -
- Out of 111 patients, 104 provided data on tumor response, showing that a significant number (78%) experienced substantial tumor regression, with correlations found between tumor response measurements and relapse-free survival rates.*
Article Synopsis
- Pancreatic adenocarcinoma (PDAC) is a challenging cancer to treat with immunotherapies, but certain intratumoral structures called tertiary lymphoid structures (TLS) have been linked to better patient survival outcomes.
- A comprehensive study analyzed 26 PDAC tumors using advanced techniques like machine learning and spatial transcriptomics to better understand the role of TLS within tumors.
- The findings revealed specific gene expression patterns in TLS that correlate with improved survival, highlighting the importance of TLS maturation and its interactions with immune cells and the tumor environment.
Article Synopsis
- PD-1 inhibitors show limited effectiveness on their own for treating hepatocellular carcinoma (HCC), but a new personalized therapeutic cancer vaccine (PTCV) may boost their efficacy by enhancing immune responses against tumors.
- In a study, a DNA plasmid PTCV combined with pembrolizumab was tested on patients with advanced HCC; the treatment was found to be relatively safe with manageable side effects and showed a 30.6% objective response rate.
- The study observed that patients with more neoantigens from the vaccine had better clinical responses, with immune profiling revealing a strong T cell response directed at tumor cells, supporting the vaccine's potential as a viable therapeutic approach.
Article Synopsis
- Neoadjuvant immunotherapy may help achieve long-term tumor remission by boosting the body's immune responses before tumor removal, and this study explores the role of tertiary lymphoid structures (TLS) in this process for liver cancer (HCC).
- The research found that neoadjuvant immunotherapy not only promotes the formation of TLS but also correlates with better treatment outcomes, including higher levels of T and B cells and improved disease-free survival.
- Notably, the study observed that as tumors regress, TLS undergo changes that indicate continued immune activity and contribute to T cell memory, which may be crucial for long-term immunity against cancer.
Article Synopsis
- * Analysis showed that 22 out of 67 SLE patients had MAVS in an aggregated form, correlating with higher serum levels of IFNβ and specific autoantibodies, unlike rheumatoid arthritis patients and healthy controls.
- * Findings suggest that these persistent MAVS aggregates could drive continuous type I IFN production, contributing to autoimmune responses in SLE patients.