Publications by authors named "Joseph Tandurella"
Pancreatic ductal adenocarcinoma (PDAC) carries an extremely poor prognosis, in part resulting from cellular heterogeneity that supports overall tumorigenicity. Cancer associated fibroblasts (CAF) are key determinants of PDAC biology and response to systemic therapy. While CAF subtypes have been defined, the effects of patient-specific CAF heterogeneity and plasticity on tumor cell behavior remain unclear.
View Article and Find Full Text PDFSuccessful 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
Article Synopsis
- Researchers developed a new method for matching chemotherapy regimens to pancreatic cancer patients based on chemosensitivity data from patient-derived organoids (PDOs).
- In a study involving PDOs from 95 patients, the method successfully matched 91% of the organoids to standard chemotherapeutics and showed that well-matched patients had significantly better clinical outcomes, such as reduced tumor markers and improved survival rates.
- The findings suggest that using PDO pharmacotyping to customize chemotherapy could lead to better treatment strategies and outcomes for patients with pancreatic ductal adenocarcinoma.
Unlabelled: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by an immunosuppressive tumor microenvironment enriched with cancer-associated fibroblasts (CAF). This study used a convergence approach to identify tumor cell and CAF interactions through the integration of single-cell data from human tumors with human organoid coculture experiments. Analysis of a comprehensive atlas of PDAC single-cell RNA sequencing data indicated that CAF density is associated with increased inflammation and epithelial-mesenchymal transition (EMT) in epithelial cells.
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- - The study involved 24 women with breast cancer, split evenly between hormone receptor-positive and advanced triple-negative types, treated with a combination of entinostat, nivolumab, and ipilimumab.
- - Results showed no severe side effects and indicated a 25% overall response rate, with better outcomes (40%) in triple-negative patients compared to hormone receptor-positive (10%).
- - The treatment yielded a 40% clinical benefit rate and a 50% progression-free survival rate at 6 months, suggesting further research in a phase II trial is warranted.
Successful pancreatic ductal adenocarcinoma (PDAC) immunotherapy necessitates optimization and maintenance of activated effector T cells (Teff). We prospectively collected and applied multi-omic analyses to paired pre- and post-treatment PDAC specimens collected in a platform neoadjuvant study of granulocyte-macrophage colony-stimulating factor-secreting allogeneic PDAC vaccine (GVAX) vaccine ± nivolumab (anti-programmed cell death protein 1 [PD-1]) to uncover sensitivity and resistance mechanisms. We show that GVAX-induced tertiary lymphoid aggregates become immune-regulatory sites in response to GVAX + nivolumab.
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- Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer that often leads to early recurrence and worse outcomes for patients.
- Research using genetically engineered mouse models and patient samples shows that TNBC tumors contain diverse cell types, including hybrid epithelial/mesenchymal (E/M) cells, which are involved in invasion and metastasis.
- The study reveals a complex activation of multiple epithelial-mesenchymal transition (EMT) programs during the metastatic process, with distinct molecular patterns observed in cancer cells as they progress from an epithelial state to hybrid and mesenchymal states, indicating various strategies for metastasis.