Dual IL-6 and CTLA-4 blockade regresses pancreatic tumors in a T cell- and CXCR3-dependent manner.

This study aimed to enhance antitumor immune responses to pancreatic cancer via Ab-based blockade of IL-6 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Mice bearing s.c.

Combined MEK/PD-L1 Inhibition Alters Peripheral Cytokines and Lymphocyte Populations Correlating with Improved Clinical Outcomes in Advanced Biliary Tract Cancer.

Purpose: Biliary tract cancers (BTC) are aggressive malignancies refractory to chemotherapy and immunotherapy. MEK inhibition (MEKi)-based regimens may have utility in this disease when combined with PD-L1 blockade. We hypothesize that dual MEK/PD-L1 inhibition alters circulating soluble and cellular immune mediators to improve clinical outcomes in patients with advanced BTC.

Finding Silver Linings: A Mixed Methods Analysis of COVID-19's Challenges and Opportunities for College Students' Functioning and Outlook.

This study examines the impact of the COVID-19 pandemic on college students' lives. A mixed methods approach, analyzing open- and closed-ended questions about challenges and opportunities, reveals numerous ways in which the pandemic has impacted students in general and differentially by gender, sexual orientation, race/ethnicity, and family income. Cisgender male and heterosexual students generally reported less of a mental health impact from the pandemic.

Multicenter randomized phase II trial of atezolizumab with or without cobimetinib in biliary tract cancers.

BACKGROUNDMEK inhibitors have limited activity in biliary tract cancers (BTCs) as monotherapy but are hypothesized to enhance responses to programmed death ligand 1 (PD-L1) inhibition.METHODSThis open-label phase II study randomized patients with BTC to atezolizumab (anti-PD-L1) as monotherapy or in combination with cobimetinib (MEK inhibitor). Eligible patients had unresectable BTC with 1 to 2 lines of prior therapy in the metastatic setting, measurable disease, and Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 1.

Expression of tdTomato and luciferase in a murine lung cancer alters the growth and immune microenvironment of the tumor.

Imaging techniques based on fluorescence and bioluminescence have been important tools in visualizing tumor progression and studying the effect of drugs and immunotherapies on tumor immune microenvironment in animal models of cancer. However, transgenic expression of foreign proteins may induce immune responses in immunocompetent syngeneic tumor transplant models and augment the efficacy of experimental drugs. In this study, we show that the growth rate of Lewis lung carcinoma (LL/2) tumors was reduced after transduction of tdTomato and luciferase (tdTomato/Luc) compared to the parental cell line.

Heat Shock Protein-90 Inhibition Alters Activation of Pancreatic Stellate Cells and Enhances the Efficacy of PD-1 Blockade in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) has a prominent fibrotic stroma, which is a result of interactions between tumor, immune and pancreatic stellate cells (PSC), or cancer-associated fibroblasts (CAF). Targeting inflammatory pathways present within the stroma may improve access of effector immune cells to PDAC and response to immunotherapy. Heat shock protein-90 (Hsp90) is a chaperone protein and a versatile target in pancreatic cancer.

Suppressive myeloid cells are expanded by biliary tract cancer-derived cytokines in vitro and associate with aggressive disease.

Background: BTC is an aggressive disease exacerbated by inflammation and immune suppression. Expansion of immunosuppressive cells occurs in biliary tract cancer (BTC), yet the role of BTC-derived cytokines in this process is unclear.

Methods: Activated signalling pathways and cytokine production were evaluated in a panel of human BTC cell lines.

Optical Control of Cytokine Signaling via Bioinspired, Polymer-Induced Latency.

Cytokine signaling is challenging to study and therapeutically exploit as the effects of these proteins are often pleiotropic. A subset of cytokines can, however, achieve signal specificity via association with latency-inducing proteins, which cage the cytokine until disrupted by discreet biological stimuli. Inspired by this precision, here, we describe a strategy for synthetic induction of cytokine latency via modification with photolabile polymers that mimic latency while attached then restore protein activity in response to light, thus controlling the magnitude, duration, and location of cytokine signals.

MEK inhibition suppresses B regulatory cells and augments anti-tumor immunity.

Mitogen-activated protein kinase (MAPK) kinase (MEK) is an integral component of the RAS pathway and a therapeutic target in RAS-driven cancers. Although tumor responses to MEK inhibition are rarely durable, MEK inhibitors have shown substantial activity and durable tumor regressions when combined with systemic immunotherapies in preclinical models of RAS-driven tumors. MEK inhibitors have been shown to potentiate anti-tumor T cell immunity, but little is known about the effects of MEK inhibition on other immune subsets, including B cells.

Preliminary analysis of resting state functional connectivity in young adults with subtypes of bipolar disorder.

Background: A precision medicine approach to bipolar disorder (BD) requires greater knowledge of neural mechanisms, especially within the BD phenotype. The present study evaluated differences in resting state functional connectivity (RSFC) between young adults followed longitudinally since childhood with full-threshold type I BD (BD-I)-characterized by distinct manic episodes-or a more sub-syndromal presentation of BD (BD Not Otherwise Specified [BD-NOS]), compared to one another and to healthy controls (HC). Independent Components Analysis (ICA), a multivariate data-driven method, and dual regression were used to explore whether connectivity within resting state networks (RSNs) differentiated the groups, especially for characteristic fronto-limbic alterations in BD.

Cognitive performance of youth with primary generalized anxiety disorder versus primary obsessive-compulsive disorder.

Background: Despite gains made in the study of childhood anxiety, differential diagnosis remains challenging because of indistinct boundaries between disorders and high comorbidity. This is certainly true for generalized anxiety disorder (GAD) and obsessive-compulsive disorder (OCD) as they share multiple cognitive processes (e.g.

Developmental evaluation of family functioning deficits in youths and young adults with childhood-onset bipolar disorder.

Background: Childhood-onset bipolar disorder (BD) is a serious condition that affects the patient and family. While research has documented familial dysfunction in individuals with BD, no studies have compared developmental differences in family functioning in youths with BD vs. adults with prospectively verified childhood-onset BD.

Preliminary mapping of the structural effects of age in pediatric bipolar disorder with multimodal MR imaging.

This study investigates multimodal structural MR imaging biomarkers of development trajectories in pediatric bipolar disorder. T1-weighted and diffusion-weighted MR imaging was conducted to investigate cross-sectional group differences with age between typically developing controls (N = 26) and youths diagnosed with bipolar disorder (N = 26). Region-based analysis was used to examine cortical thickness of gray matter and diffusion tensor parameters in superficial white matter, and tractography-based analysis was used to examine deep white matter fiber bundles.