Integrin αE(CD103) Is Involved in Regulatory T-Cell Function in Allergic Contact Hypersensitivity

Murine contact hypersensitivity (CHS) is a dendritic cell (DC)-dependent T-cell-mediated inflammation with CD8+ T cells as effectors and CD4+ T cells as regulators (Treg cells) that models human allergic contact dermatitis. The integrin αE(CD103) is expressed by some T-cell and DC subsets and has been implicated in epithelial lymphocyte localization, but its role in immune regulation remains enigmatic. We have identified a function for CD103 in the development of cutaneous allergic immune responses. CHS responses, but not irritant contact dermatitis, were significantly augmented in CD103-deficient mice in hapten-challenged skin. Phenotype and function of skin DCs during sensitization were normal, whereas adoptive transfer experiments revealed that the elevated CHS response in CD103-deficient mice is transferred by primed T cells and is independent of resident cells in recipient mice. While T-cell counts were elevated in challenged skin of CD103-deficient mice, the FoxP3 expression level of CD4+CD25+ Treg cells was significantly reduced, indicating impaired functionality. Indeed, Treg cells from CD103-deficient mice were not able to suppress CHS reactions during the elicitation phase. Further, CD103 on FoxP3+ Treg cells was involved in Treg retention to inflamed skin. These findings indicate an unexpected dichotomous functional role for CD103 on Treg cells by modulating FoxP3 expression

Comprehensive genomic profiles of small cell lung cancer

We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Dex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer

Impact of COVID-19 crisis on medical care of patients with metastasized uro-oncologic disease under systemic cancer therapy: a multicenter study in German university hospitals

Purpose!#!To date, over 4.2 million Germans and over 235 million people worldwide have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Uro-oncology (UO) patients are particularly vulnerable but in urgent need of life-saving systemic treatments. Our multicentric study examined the impact of the COVID-19 crisis on the medical care of UO patients in German university hospitals receiving ongoing systemic anti-cancer treatment and to detect the delay of medical care, defined as deferred medical treatment or deviation of the pre-defined follow-up assessment.!##!Methods!#!Data of 162 UO patients with metastatic disease undergoing systemic cancer treatment at five university hospitals in Germany were included in our analyses. The focus of interest was any delay or change in treatment between February 2020 and May 2020 (first wave of the COVID-19 crisis in Germany). Statistical analysis of contingency tables were performed using Pearson's chi-squared and Fisher's exact tests, respectively. Effect size was determined using Cramér's V (V).!##!Results!#!Twenty-four of the 162 patients (14.8%) experienced a delay in systemic treatment of more than 2 weeks. Most of these received immuno-oncologic (IO) treatments (13/24, 54.2%, p = 0.746). Blood tests were delayed or canceled significantly more often in IO patients but with a small effect size (21.1%, p = 0.042, V = 0.230). Treatment of patients with renal cell carcinoma (12/73, 16.4%) and urothelial carcinoma (7/32, 21.9%) was affected the most.!##!Conclusions!#!Our data show that the COVID-19 pandemic impacted the medical care of UO patients, but deferment remained modest. There was a tendency towards delays in IO and ADT treatments in particular

Tree data set from forest inventories in north-eastern Siberia - Tree measurements

The data set presents more than 12,000 of about 40,000 trees, which were surveyed during several Russian-German expeditions by the North-Eastern Federal University Yakutsk and the Alfred-Wegener-Institute Potsdam in the North-East of the Russian Federation between the years 2011 and 2021. The purpose was to gather information on trees and forests in this region, which was then used to understand tree line migration, stand infilling and natural disturbance and succession processes and to initialize and validate a forest model. Trees are located on more than 160 vegetation plots, each of which has a size of several hundred square meters. For every tree, height was estimated, and the species recorded. Some individuals were subject to more detailed inventory, including diameters at base and at breast height, crown diameters, and other information. This table partially overlaps with the data set: “Tree data set from forest inventories in north-eastern Siberia - Tree heights.” (doi: 10.1594/PANGAEA.949863), but includes all tree measurements as well as all inventoried trees, which were not included in the Tree heights dataset due to small or lying deadwood

Tree data set from forest inventories in north-eastern Siberia

The data set presents about 40,000 trees which where surveyed during several Russian-German expeditions by North-Eastern Federal University Yakutsk and Alfred-Wegener-Institute Potsdam to the North-East of the Russian Federation between the years 2011 and 2021. The purpose was to gather information on trees and forests in this region, which was then used to understand tree line migration, stand infilling and natural disturbance and succession processes and to initialize and validate a forest model. Trees are located on more than 160 vegetation plots, each of which has a size of several hundred square meters. For every tree, height was estimated, and the species recorded. Some individuals were subject to more detailed inventory, including diameters at base and at breast height, crown diameters, and other information

Tree data set from forest inventories in north-eastern Siberia - Tree heights

The data set presents more than 32,000 of about 40,000 trees, which were surveyed during several Russian-German expeditions by the North-Eastern Federal University Yakutsk and the Alfred-Wegener-Institute Potsdam in the North-East of the Russian Federation between the years 2011 and 2021. The purpose was to gather information on trees and forests in this region, which was then used to understand tree line migration, stand infilling and natural disturbance and succession processes and to initialize and validate a forest model. Trees are located on more than 160 vegetation plots, each of which has a size of several hundred square meters. For every tree, height was estimated, and the species recorded, while a few individuals were subject to more detailed inventory. This table contains every standing tree of at least 40 cm height that was encountered on the vegetation plots described in the Plot Data Base. It partially overlaps with the dataset “Tree data set from forest inventories in north-eastern Siberia - Tree measurements.” (doi: 10.1594/PANGAEA.949861), which additionally contains details on small or lying deadwood