CXCL12-targeted immunomodulatory gene therapy reduces radiation-induced fibrosis in healthy tissues.

Radiation-induced fibrosis (RIF) is a progressive pathology deleteriously impacting cancer survivorship. CXCL12 is an immune-stromal signal implicated in fibrosis and innate response. We hypothesised that modulation of CXCL12 would phenotypically mitigate RIF.

A survey on autonomous environmental monitoring approaches: towards unifying active sensing and reinforcement learning.

The environmental pollution caused by various sources has escalated the climate crisis making the need to establish reliable, intelligent, and persistent environmental monitoring solutions more crucial than ever. Mobile sensing systems are a popular platform due to their cost-effectiveness and adaptability. However, in practice, operation environments demand highly intelligent and robust systems that can cope with an environment's changing dynamics.

Modelling bronchial epithelial-fibroblast cross-talk in idiopathic pulmonary fibrosis (IPF) using a human-derived in vitro air liquid interface (ALI) culture.

Idiopathic Pulmonary Fibrosis (IPF) is a devastating form of respiratory disease with a life expectancy of 3-4 years. Inflammation, epithelial injury and myofibroblast proliferation have been implicated in disease initiation and, recently, epithelial-fibroblastic crosstalk has been identified as a central driver. However, the ability to interrogate this crosstalk is limited due to the absence of in vitro models that mimic physiological conditions.

Durable responses to ATR inhibition with ceralasertib in tumors with genomic defects and high inflammation.

BACKGROUNDPhase 1 study of ATRinhibition alone or with radiation therapy (PATRIOT) was a first-in-human phase I study of the oral ATR (ataxia telangiectasia and Rad3-related) inhibitor ceralasertib (AZD6738) in advanced solid tumors.METHODSThe primary objective was safety. Secondary objectives included assessment of antitumor responses and pharmacokinetic (PK) and pharmacodynamic (PD) studies.

Measuring the foveal avascular zone in diabetes: A study using optical coherence tomography angiography.

Aims/introduction: Diabetes is a global issue that currently affects 425 million people worldwide. One observable microvascular complication of this condition is a change in the foveal avascular zone (FAZ). In this study, we used optical coherence tomography angiography to investigate the effect of diabetes on the FAZ.

Quantitative Assessment and Prognostic Associations of the Immune Landscape in Ovarian Clear Cell Carcinoma.

Ovarian clear cell carcinoma (OCCC) is a rare subtype of epithelial ovarian cancer characterised by a high frequency of loss-of-function mutations and a poor response to chemotherapy. Despite their generally low mutational burden, an intratumoural T cell response has been reported in a subset of OCCC, with purported to be a biomarker for the response to the immune checkpoint blockade independent of micro-satellite instability (MSI). However, assessment of the different immune cell types and spatial distribution specifically within OCCC patients has not been described to date.

Differential and longitudinal immune gene patterns associated with reprogrammed microenvironment and viral mimicry in response to neoadjuvant radiotherapy in rectal cancer.

Background: Rectal cancers show a highly varied response to neoadjuvant radiotherapy/chemoradiation (RT/CRT) and the impact of the tumor immune microenvironment on this response is poorly understood. Current clinical tumor regression grading systems attempt to measure radiotherapy response but are subject to interobserver variation. An unbiased and unique histopathological quantification method (change in tumor cell density (ΔTCD)) may improve classification of RT/CRT response.

Proteomics of REPLICANT perfusate detects changes in the metastatic lymph node microenvironment.

In breast cancer (BC), detecting low volumes of axillary lymph node (ALN) metastasis pre-operatively is difficult and novel biomarkers are needed. We recently showed that patient-derived ALNs can be sustained ex-vivo using normothermic perfusion. We now compare reactive (tumour-free; n = 5) and macrometastatic (containing tumour deposits >2 mm; n = 4) ALNs by combining whole section multiplex immunofluorescence with TMT-labelled LC-MS/MS of the circulating perfusate.

Sub-clinical thickening of the fovea in diabetes and its relationship to glycaemic control: a study using swept-source optical coherence tomography.

Background: Accumulation of multiple pockets of fluid at the fovea, as a complication of poor blood glucose control in diabetes, causes impairment of central vision. A new ability to demonstrate a pre-clinical phase of this maculopathy could be valuable, enabling diabetic individuals to be alerted to the need to improve their glycaemic control. This study aimed to use swept-source optical coherence tomography (SS-OCT) to measure foveal thickness and macular volume in diabetic individuals without cystoid macular oedema, and in non-diabetic individuals, and relate these measures to participants' glycaemic control.

Immune landscape, evolution, hypoxia-mediated viral mimicry pathways and therapeutic potential in molecular subtypes of pancreatic neuroendocrine tumours.

Objective: A comprehensive analysis of the immune landscape of pancreatic neuroendocrine tumours (PanNETs) was performed according to clinicopathological parameters and previously defined molecular subtypes to identify potential therapeutic vulnerabilities in this disease.

Design: Differential expression analysis of 600 immune-related genes was performed on 207 PanNET samples, comprising a training cohort (n=72) and two validation cohorts (n=135) from multiple transcriptome profiling platforms. Different immune-related and subtype-related phenotypes, cell types and pathways were investigated using different in silico methods and were further validated using spatial multiplex immunofluorescence.

Author Correction: STING and IRF3 in stromal fibroblasts enable sensing of genomic stress in cancer cells to undermine oncolytic viral therapy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Prostate-specific membrane antigen expression in melanoma metastases.

Background: Prostate-specific membrane antigen (PSMA) is a prostatic epithelial protein that is used as a radiotracer (68Ga-PSMA-11) for prostate cancer staging. PSMA-PET/CT (positron emission tomography/computed tomography) performed for prostate cancer has been observed to detect melanoma metastases. The aim of this study was to investigate the performance of PSMA immunohistochemistry on resected melanoma metastases to explore its use as a diagnostic imaging biomarker for melanoma.

STING and IRF3 in stromal fibroblasts enable sensing of genomic stress in cancer cells to undermine oncolytic viral therapy.

Cancer-associated fibroblasts (CAFs) perform diverse roles and can modulate therapy responses. The inflammatory environment within tumours also influences responses to many therapies, including the efficacy of oncolytic viruses; however, the role of CAFs in this context remains unclear. Furthermore, little is known about the cell signalling triggered by heterotypic cancer cell-fibroblast contacts and about what activates fibroblasts to express inflammatory mediators.

Computational Image Analysis of T-Cell Infiltrates in Resectable Gastric Cancer: Association with Survival and Molecular Subtypes.

Background: Gastric and gastro-esophageal junction cancers (GCs) frequently recur after resection, but markers to predict recurrence risk are missing. T-cell infiltrates have been validated as prognostic markers in other cancer types, but not in GC because of methodological limitations of past studies. We aimed to define and validate the prognostic role of major T-cell subtypes in GC by objective computational quantification.

Combination therapy with oncolytic viruses and immune checkpoint inhibitors.

: Immune checkpoint inhibitors (ICI) have dramatically improved the outcome for cancer patients across multiple tumor types. However the response rates to ICI monotherapy remain relatively low, in part due to some tumors cultivating an inherently 'cold' immune microenvironment. Oncolytic viruses (OV) have the capability to promote a 'hotter' immune microenvironment which can improve the efficacy of ICI.

Development of a new fusion-enhanced oncolytic immunotherapy platform based on herpes simplex virus type 1.

Background: Oncolytic viruses preferentially replicate in tumors as compared to normal tissue and promote immunogenic cell death and induction of host systemic anti-tumor immunity. HSV-1 was chosen for further development as an oncolytic immunotherapy in this study as it is highly lytic, infects human tumor cells broadly, kills mainly by necrosis and is a potent activator of both innate and adaptive immunity. HSV-1 also has a large capacity for the insertion of additional, potentially therapeutic, exogenous genes.

Phase I Trial of an ICAM-1-Targeted Immunotherapeutic-Coxsackievirus A21 (CVA21) as an Oncolytic Agent Against Non Muscle-Invasive Bladder Cancer.

Purpose: The CANON [VATAK in -muscle-invasive bladder cancer (NMIBC)] study evaluated a novel ICAM-1-targeted immunotherapeutic-coxsackievirus A21 as a novel oncolytic agent against bladder cancer.

Patients And Methods: Fifteen patients enrolled in this "window of opportunity" phase I study, exposing primary bladder cancers to CAVATAK prior to surgery. The first 9 patients received intravesical administration of monotherapy CAVATAK; in the second stage, 6 patients received CAVATAK with a subtherapeutic dose of mitomycin C, known to enhance expression of ICAM-1 on bladder cancer cells.

CEA expression heterogeneity and plasticity confer resistance to the CEA-targeting bispecific immunotherapy antibody cibisatamab (CEA-TCB) in patient-derived colorectal cancer organoids.

Background: The T cell bispecific antibody cibisatamab (CEA-TCB) binds Carcino-Embryonic Antigen (CEA) on cancer cells and CD3 on T cells, which triggers T cell killing of cancer cell lines expressing moderate to high levels of CEA at the cell surface. Patient derived colorectal cancer organoids (PDOs) may more accurately represent patient tumors than established cell lines which potentially enables more detailed insights into mechanisms of cibisatamab resistance and sensitivity.

Methods: We established PDOs from multidrug-resistant metastatic CRCs.

PD-1 Blockade Following Isolated Limb Perfusion with Vaccinia Virus Prevents Local and Distant Relapse of Soft-tissue Sarcoma.

Purpose: The prevention and treatment of metastatic sarcoma are areas of significant unmet need. Immune checkpoint inhibitor monotherapy has shown little activity in sarcoma and there is great interest in identifying novel treatment combinations that may augment responses. and , we investigated the potential for an oncolytic vaccinia virus (GLV-1h68) delivered using isolated limb perfusion (ILP) to promote antitumor immune responses and augment response to PD-1 blockade in sarcoma.

Clinical and genetic heterogeneity in Melkersson-Rosenthal Syndrome.

Melkersson Rosenthal syndromes (MRS) is a rare autosomal dominantly inherited neurocutaneous syndrome characterised by a triad of facial (seventh cranial) nerve palsy, recurrent orofacial swelling and fissuring of the tongue. A recent report implicated a heterozygous missense variant in SLC27A1 (FATP1) as the cause of this condition in members of an affected Chinese family. We undertook Sanger sequencing of this gene in 14 affected unrelated individuals affected by MRS.

Measuring visual cortical oxygenation in diabetes using functional near-infrared spectroscopy.

Aims: Diabetes mellitus affects about 6% of the world's population, and the chronic complications of the disease may result in macro- and micro-vascular changes. The purpose of the current study was to shed light on visual cortical oxygenation in diabetic individuals. We then aimed to compare the haemodynamic response (HDR) to visual stimulation with glycaemic control, given the likelihood of diabetic individuals suffering from such macro- and micro-vascular insult.