(2018) Neuropathology and Applied Neurobiology 44, 185-206 Tumour-associated microglia/macrophages predict poor prognosis in high-grade gliomas and correlate with an aggressive tumour subtype Aims: Glioblastomas are highly aggressive and treatment resistant. Increasing evidence suggests that tumour-associated macrophages/microglia (TAMs) facilitate tumour progression by acquiring a M2-like phenotype. Our objective was to investigate the prognostic value of TAMs in gliomas using automated quantitative double immunofluorescence. Methods: Samples from 240 patients with primary glioma were stained with antibodies against ionized calcium-binding adaptor molecule-1 (IBA-1) and cluster of differentiation 204 (CD204) to detect TAMs and M2-like TAMs. The expression levels were quantified by software-based classifiers. The associations between TAMs, gemistocytic cells and glioblastoma subtype were examined with immuno-and haematoxylin-eosin stainings. Three tissue arrays containing glioblastoma specimens were included to study IBA-1/CD204 levels in central tumour and tumour periphery and to characterize CD204 + cells. Results: Our data revealed that the amount of especially CD204 + TAMs increases with malignancy grade. In grade III-IV, high CD204 expression was associated with shorter survival, while high IBA-1 intensity correlated with a longer survival. In grade IV, CD204 showed independent prognostic value when adjusting for clinical data and the methylation status of O6-methylguanine-DNA methyltransferase. Our findings were confirmed in two bioinformatics databases. TAMs were more abundant in central tumour tissue, mesenchymal glioblastomas and gliomas with many gemistocytic cells. CD204 + TAMs coexpressed proteins related to tumour aggressiveness including matrix metallopeptidase-14 and hypoxiainducible factor-1a. Conclusions: This is the first study to use automated quantitative immunofluorescence to determine the prognostic impact of TAMs. Our results suggest that M2-like TAMs hold an unfavourable prognostic value in high-grade gliomas and may contribute to a pro-tumourigenic microenvironment.

Summary Stem cells reside in niches that regulate the balance between self-renewal and differentiation. The identity of a stem cell is linked with the ability to interact with its niche through adhesion mechanisms. To identify targets that disrupt cancer stem cell (CSC) adhesion, we performed a flow cytometry screen on patient derived glioblastoma (GBM) cells and identified junctional adhesion molecule-A (JAM-A) as a CSC adhesion mechanism essential for self-renewal and tumor growth. JAM-A was dispensable for normal neural stem/progenitor cell (NPC) function and JAM-A expression was reduced in normal brain versus GBM. Targeting JAM-A compromises the self-renewal of CSCs. JAM-A expression negatively correlated to GBM patient prognosis. Our results demonstrate that novel GBM targeting strategies can be identified through screening adhesion receptors and JAM-A represents a novel mechanism for niche driven CSC maintenance.

Background: The COVID-19 pandemic is an international public health crisis. The risk of getting an infection with COVID-19 might impact the emotional well-being in patients with cancer. The aim of this study was to investigate quality of life (QoL) for patients with cancer during the COVID-19 pandemic. Patients and methods: A cross-sectional survey, including questions about demographics, concerns of COVID-19 impact on cancer treatment and outpatient clinic visits, and the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire was sent to patients with cancer at the