Publications by authors named "Gregor Werba"

Article Synopsis
  • The study investigates the effects of blocking IL1β in combination with PD1 blockade and chemotherapy on myeloid immunosuppression and T-cell responses in patients with advanced pancreatic cancer.
  • Results showed a slight increase in activated CD8+ T cells and a reduction in myeloid-derived suppressor cells (MDSCs) in the blood of trial patients compared to those receiving standard chemotherapy.
  • However, changes in the tumor microenvironment were minimal, suggesting that larger studies are needed to fully understand the impacts of these treatments on tumor immunity.
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Article Synopsis
  • - PDAC (pancreatic ductal adenocarcinoma) often shows mutations in repair proteins, affecting 20%-25% of cases, which results in a vulnerability to certain cancer treatments but also leads to therapy resistance in many patients.
  • - The enzyme polymerase theta (POLQ) helps repair DNA through a process called microhomology-mediated end-joining and is overexpressed when homologous recombination processes are inactive, which is common in PDAC cases with mutations in BRCA1 and BRCA2.
  • - In studies, knocking down POLQ proved to be synthetically lethal in HR-deficient PDAC models, promoting immune responses and enhancing infiltration of CD8+ T cells, indicating POLQ's
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Hepato-pancreatico-biliary (HPB) malignancies are difficult-to-treat and continue to to have a high mortality and significant therapeutic resistance to standard therapies. Immune oncology (IO) therapies have demonstrated efficacy in several solid malignancies when combined with chemotherapy, whereas response rates in pancreatic ductal adenocarcinoma (PDA) are poor. While promising in hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), there remains an unmet need to fully leverage IO therapies to treat HPB tumors.

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The tumor microenvironment (TME) in pancreatic ductal adenocarcinoma (PDAC) is a complex ecosystem that drives tumor progression; however, in-depth single cell characterization of the PDAC TME and its role in response to therapy is lacking. Here, we perform single-cell RNA sequencing on freshly collected human PDAC samples either before or after chemotherapy. Overall, we find a heterogeneous mixture of basal and classical cancer cell subtypes, along with distinct cancer-associated fibroblast and macrophage subpopulations.

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Response to cancer immunotherapy in primary versus metastatic disease has not been well-studied. We found primary pancreatic ductal adenocarcinoma (PDA) is responsive to diverse immunotherapies whereas liver metastases are resistant. We discovered divergent immune landscapes in each compartment.

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Transcriptional heterogeneity among malignant cells of a tumor has been studied in individual cancer types and shown to be organized into cancer cell states; however, it remains unclear to what extent these states span tumor types, constituting general features of cancer. Here, we perform a pan-cancer single-cell RNA-sequencing analysis across 15 cancer types and identify a catalog of gene modules whose expression defines recurrent cancer cell states including 'stress', 'interferon response', 'epithelial-mesenchymal transition', 'metal response', 'basal' and 'ciliated'. Spatial transcriptomic analysis linked the interferon response in cancer cells to T cells and macrophages in the tumor microenvironment.

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Background: Historically, robotic surgery incurs longer operative times, higher costs, and nonsuperior outcomes compared with laparoscopic surgery. However, in areas of limited visibility and decreased accessibility such as the gastroesophageal junction, robotic platforms may improve visualization and facilitate dissection. This study compares 30-day outcomes between robotic-assisted foregut surgery (RAF) and laparoscopic-assisted foregut surgery in the Veterans Health Administration.

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The gut microbiome shapes local and systemic immunity. The liver is presumed to be a protected sterile site. As such, a hepatic microbiome has not been examined.

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Background: Preoperative biliary drainage (PBD) has been advocated to address the plethora of physiologic derangements associated with cholestasis. However, available literature reports mixed outcomes and is based on largely outdated and/or single-institution studies.

Methods: Patients undergoing PBD prior to pancreaticoduodenectomy (PD) for periampullary malignancy between 2014-2018 were identified in the ACS-NSQIP pancreatectomy dataset.

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Background: Morbidity after Pancreaticoduodenectomy (PD) has remained unchanged over the past decade. Delayed Gastric Emptying (DGE) is a major contributor with significant impact on healthcare-costs, quality of life and, for malignancies, even survival. We sought to develop a scoring system to aid in easy preoperative identification of patients at risk for DGE.

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Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related mortality in the United States and has only recently achieved a 5-yr survival rate of 10%. This dismal prognosis reflects the remarkable capacity of PDAC to effectively adapt to and resist therapeutic intervention. In this review, we discuss recent advances in our understanding of the biological underpinnings of PDAC and their implications as targetable vulnerabilities in this highly lethal disease.

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Pancreatic ductal adenocarcinoma (PDAC) features a hostile tumor microenvironment (TME) that renders it remarkably resistant to most therapeutic interventions. Consequently, survival remains among the poorest compared with other gastrointestinal cancers. Concerted efforts are underway to decipher the complex PDAC TME, break down barriers to efficacious therapies and identify novel treatment strategies.

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Background: Video-assisted thoracoscopic surgery (VATS) offers reduced morbidity compared with open thoracotomy (OT) for pulmonary surgery. The use of VATS over time has increased, but at a modest rate in civilian populations. This study examines temporal trends in VATS use and compares outcomes between VATS and OT in the Veterans Health Administration (VHA).

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Objective: Mediastinal masses are commonly encountered by the thoracic surgeon. Few studies have reported on the frequency and characteristics of symptoms at presentation. The primary objective of this study is to determine how often patients present with symptoms from a mediastinal mass.

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Background: Previous literature in other surgical disciplines regarding the impact of resident and fellow involvement on operative time and outcomes has yielded mixed results. The impact of trainee involvement on minimally invasive thoracic surgery is unknown. This study compared risk-adjusted differences in operative time and outcomes of video-assisted thoracoscopic lobectomy for cancer between cases performed with and without residents and fellows involved.

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Piezo1 is a mechanosensitive ion channel that has gained recognition for its role in regulating diverse physiological processes. However, the influence of Piezo1 in inflammatory disease, including infection and tumor immunity, is not well studied. We postulated that Piezo1 links physical forces to immune regulation in myeloid cells.

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Programmed cell death protein 1 (PD-1) ligation delimits immunogenic responses in T cells. However, the consequences of programmed cell death 1 ligand 1 (PD-L1) ligation in T cells are uncertain. We found that T cell expression of PD-L1 in cancer was regulated by tumor antigen and sterile inflammatory cues.

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Background: Vascular reconstruction during pancreaticoduodenectomy is increasingly utilized to improve pancreatic cancer resectability. However, few multi-institutional studies have evaluated the morbidity and mortality of arterial and venous reconstruction during this procedure.

Methods: A retrospective analysis was performed utilizing the targeted pancreas module of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) for pancreaticoduodenectomy from 2014 to 2015.

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