CD137 agonism enhances anti-PD1 induced activation of expanded CD8 T cell clones in a neoadjuvant pancreatic cancer clinical trial.

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.

Maturation of Tertiary Lymphoid Structures.

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.

Immunotherapy response induces divergent tertiary lymphoid structure morphologies in hepatocellular carcinoma.

Tertiary 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.

PanIN and CAF transitions in pancreatic carcinogenesis revealed with spatial data integration.

This study introduces a new imaging, spatial transcriptomics (ST), and single-cell RNA-sequencing integration pipeline to characterize neoplastic cell state transitions during tumorigenesis. We applied a semi-supervised analysis pipeline to examine premalignant pancreatic intraepithelial neoplasias (PanINs) that can develop into pancreatic ductal adenocarcinoma (PDAC). Their strict diagnosis on formalin-fixed and paraffin-embedded (FFPE) samples limited the single-cell characterization of human PanINs within their microenvironment.

Transfer Learning Reveals Cancer-Associated Fibroblasts Are Associated with Epithelial-Mesenchymal Transition and Inflammation in Cancer Cells in 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.

Systems immunology spanning tumors, lymph nodes, and periphery.

The immune system defines a complex network of tissues and cell types that orchestrate responses across the body in a dynamic manner. The local and systemic interactions between immune and cancer cells contribute to disease progression. Lymphocytes are activated in lymph nodes, traffic through the periphery, and impact cancer progression through their interactions with tumor cells.

Uncovering the spatial landscape of molecular interactions within the tumor microenvironment through latent spaces.

Recent advances in spatial transcriptomics (STs) enable gene expression measurements from a tissue sample while retaining its spatial context. This technology enables unprecedented in situ resolution of the regulatory pathways that underlie the heterogeneity in the tumor as well as the tumor microenvironment (TME). The direct characterization of cellular co-localization with spatial technologies facilities quantification of the molecular changes resulting from direct cell-cell interaction, as it occurs in tumor-immune interactions.

Integrated T cell cytometry metrics for immune-monitoring applications in immunotherapy clinical trials.

Mass cytometry, or cytometry by TOF (CyTOF), provides a robust means of determining protein-level measurements of more than 40 markers simultaneously. While the functional states of immune cells occur along continuous phenotypic transitions, cytometric studies surveying cell phenotypes often rely on static metrics, such as discrete cell-type abundances, based on canonical markers and/or restrictive gating strategies. To overcome this limitation, we applied single-cell trajectory inference and nonnegative matrix factorization methods to CyTOF data to trace the dynamics of T cell states.

Entinostat Decreases Immune Suppression to Promote Antitumor Responses in a HER2+ Breast Tumor Microenvironment.

Therapeutic combinations to alter immunosuppressive, solid tumor microenvironments (TME), such as in breast cancer, are essential to improve responses to immune checkpoint inhibitors (ICI). Entinostat, an oral histone deacetylase inhibitor, has been shown to improve responses to ICIs in various tumor models with immunosuppressive TMEs. The precise and comprehensive alterations to the TME induced by entinostat remain unknown.

Wild primate microbiomes prevent weight gain in germ-free mice.

Background: The gut microbiome harbors trillions of bacteria that play a major role in dietary nutrient extraction and host metabolism. Metabolic diseases such as obesity and diabetes are associated with shifts in microbiome composition and have been on the rise in Westernized or highly industrialized countries. At the same time, Westernized diets low in dietary fiber have been shown to cause loss of gut microbial diversity.

Synchronous Bilateral Carcinoma of the Ureters. Report of a Case and a Short Discussion of the Literature.

Background/aim: The strategy for treatment of bilateral simultaneous renal pelvic and/or ureteral tumors has not been established and is dependent on individual decision.

Case Report: We herein report the case of an elderly man who was examined for fatigue at the emergency department and subsequently diagnosed with bilateral ureteral cancer. The most common histologic type of ureteral cancer is urothelial (transitional epithelium) cancer and though it is rare, it can be synchronously present in the contralateral ureter.

Fecal microbiota transplantation reverses antibiotic and chemotherapy-induced gut dysbiosis in mice.

Fecal microbiota transplantation (FMT) is now widely used to treat recurrent Clostridium difficile infection, but has been less studied as a means to restore microbiome diversity and composition following antibiotic or chemotherapy treatments. The purpose of our study was to assess the efficacy of FMT to reverse antibiotic- and chemotherapy-induced gut dysbiosis in a mouse model. C57BL/6J mice were treated with ampicillin for 1 week and/or received a single intraperitoneal injection of 5-Fluorouracil.

Renal emphysema in diabetic patients: CT evaluation.

Renal emphysema is a rare, fulminant, suppurative infection of pelvicaliceal system, renal parenchyma, perinephric tissues, and retroperitoneum. It is characterized by formation of gas. Invariably this condition is associated with diabetes mellitus and carries high mortality (40-90%).

Sonographic evaluation of epignathus.

Epignathus is extremely rare form of teratoid tumor arising from the palate or pharynx in the region of basisphenoid (Rathke's pouch), filling the buccal cavity and protruding from the mouth. This tumor usually causes death in neonatal life because of its location and because surgical removal is often impossible. Prenatal sonographic diagnosis is important for genetic counseling, obstetric management and in some cases neonatal surgery.

CT guided percutaneous adrenal biopsy for lesions with equivocal findings in chemical shift MR imaging.

Purpose: The aim of this study was to evaluate the usefulness of CT guided adrenal biopsy in patients with equivocal MR chemical shift imaging findings.

Material And Methods: Fifty seven patients, 32 with history of malignancy and 25 without history of malignancy, 30 men and 27 women (33-82 years, mean age:58.8 years), with equivocal findings in chemical shift MR imaging, were subjected to CT guided percutaneous adrenal biopsy.

Pneumosinus Dilatans Syndrome of the Sphenoid Sinus. A CT Evaluation.

This study discusses the CT findings of pneumosinus dilatans of the sphenoid sinus, highlighting the clinically important CT characteristics. The CT findings of 26 patients with overpneumatization of the sphenoid sinus are presented in correlation with the clinical findings. Twenty-two patients had overpneumatization beyond the boundaries of the body of the sphenoid bone with or without bone remodelling but only two patients reported headaches.

MRI evaluation of diastematomyelia and associated abnormalities.

Fourteen children were studied with a 1Tesla scanner to assess the role of magnetic resonance (MR) imaging in the recognition and evaluation of diastematomyelia and associated abnormalities. With MRI divided spinal cord was well imaged in its entire craniocaudal extent. Fibrous bands or bony septum when it contained a marrow cavity, were also well depicted.

Stimulation of phospholipase C by guanine-nucleotide-binding protein beta gamma subunits.

We have previously shown that soluble fractions obtained from human HL-60 granulocytes contain a phospholipase C which is markedly stimulated by the stable GTP analogue guanosine 5'-[3-O-thio]triphosphate (Camps, M., Hou, C., Jakobs, K.

Outcome of 100 randomly positioned children of very low birthweight at 2 years.

Prematurely born children often show a tendency to adopt extensor motor patterns during the first years of life. These children and especially those children of very low birthweight are considered to be at high risk for abnormal development. Positioning in an ordinary manner or in a more flexed position imposed at random during the neonatal period until discharge from hospital did not have a statistically significant influence on the development of these children at 24 months after term.