Publications by authors named "D Sidiropoulos"
Successful pancreatic ductal adenocarcinoma (PDAC) immunotherapy requires therapeutic combinations that induce quality T cells. Tumor microenvironment (TME) analysis following therapeutic interventions can identify response mechanisms, informing design of effective combinations. We provide a reference single-cell dataset from tumor-infiltrating leukocytes (TILs) from a human neoadjuvant clinical trial comparing the granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting allogeneic PDAC vaccine GVAX alone, in combination with anti-PD1 or with both anti-PD1 and CD137 agonist.
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- * In a Phase II clinical trial, 27 patients received entinostat followed by nivolumab, resulting in an objective response rate of 11% and a median response duration of over 10 months, although the primary endpoint for overall effectiveness was not reached.
- * The combination treatment led to significant immune profile changes, including increased dendritic cell activity and enhanced inflammatory response, suggesting potential for improving treatment strategies in PDA despite
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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- 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.