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Immune checkpoint inhibitors (ICI) have revolutionized the treatment landscape of advanced malignancies, but come with a diverse spectrum of immune-related adverse events (irAEs). Mechanistic studies can aid the transition from expert-opinion to evidence-based irAE treatment strategies. We aimed to longitudinally characterize peripheral blood T and B cell dynamics in ICI-treated patients by multicolor flow cytometry and serum multiplex immunoassay at baseline, ±3 weeks and ±6 weeks or upon clinically relevant irAEs. We analyzed samples from 44 ICI-treated patients (24 anti-PD-1 monotherapy, 20 combined anti-PD-1/anti-CTLA-4; cICI), of whom 21 developed irAEs, and 10 healthy donors. IrAEs after cICI were characterized by significantly enhanced proliferation of Th1-associated, mainly (CD4+) effector memory T cells, as well as Th17-associated immune responses and germinal center activation (reflected by CXCL13 and IL-21 increases). We observed no changes in CD21lo, memory, class-switched or newly activated B cell subsets. Especially double-positive PD-1+LAG-3+CD8+T cells showed enhanced cytotoxic capacity in patients with irAEs after cICI. Within anti-PD-1 monotherapy, irAEs were associated with modestly enhanced Th1-associated responses reflected by increased serum CXCL9 and CXCL10. In conclusion, ICI-induced toxicity is dominated by enhanced Th1-associated responses, but in cICI we also found evidence for Th17-associated responses and germinal center activation. Together, our data add to the growing body of evidence that irAEs may be driven by newly activated CD4+helper T cells, specifically after cICI. This study also supports tailored irAE treatment, based on ICI regimen, and to deploy specific strategies such as Th17 inhibition especially in cICI-associated irAEs.

Aim of the study Patients with cancer might have an increased risk for severe outcome of coronavirus disease 2019 (COVID-19). To identify risk factors associated with a worse outcome of COVID-19, a nationwide registry was developed for patients with cancer and COVID-19. Methods This observational cohort study has been designed as a quality of care registry and is executed by the Dutch Oncology COVID-19 Consortium (DOCC), a nationwide collaboration of oncology physicians in the Netherlands. A questionnaire has been developed to collect pseudonymised patient data on patients’ characteristics, cancer diagnosis, and treatment. All patients with COVID-19 and a cancer diagnosis or treatment in the past 5 years are eligible. Results Between March 27th and May 4th, 442 patients were registered. For this first analysis, 351 patients were included of whom 114 patients died. In multivariable analyses, age ≥65 years (p, Highlights • Patients with cancer might have an increased risk for severe outcome of COVID-19. • This nationwide study investigated risk factors for fatal outcome of COVID-19. • Among 442 registered patients with cancer, 32.3% of patients died of COVID-19. • Haematological malignancy and lung cancer increased the risk of fatal outcome. • These results can guide treatment and vaccination decisions in patients with cancer.

Objective Adipose tissue surrounding coronary arteries may contribute to the development of coronary atherosclerosis given its localisation and potential for local production of inflammatory cytokines. We compared various measurements for quantifying epicardial adipose tissue (EAT) and peri-coronary fat using cardiac CT. Additionally, we estimated their relationship with obesity and metabolic syndrome in patients suspected of coronary artery disease (CAD). Methods EAT and peri-coronary fat measurements were performed on cardiac multi-slice CT scans in 60 patients (aged 50–70 years) referred for coronary angiography. EAT was measured as thickness on the right ventricular free wall, as area at the base of the ventricles, and as volume. Peri-coronary fat was assessed as thickness and cross-sectional area surrounding the three main coronary arteries. Linear regression analysis was used to assess the relation of EAT and peri-coronary fat with obesity and metabolic syndrome (ATPIII criteria). Results Volumetric EAT measurements showed good reproducibility with low coefficients of variation (CVs) varying between 3.0% and 5.0%. Measurements of EAT and peri-coronary fat thickness and area were moderately reproducible (CVs 11.0–23.4%). The amount of EAT and peri-coronary fat (per standard deviation) was related with obesity (BMI ≥30kg/m 2 ) ( β 1.24; 95% CI 0.66; 1.81) and metabolic syndrome ( β 0.81; 95% CI 0.28; 1.33). Conclusions Volumetric quantification of EAT using cardiac CT is highly reproducible compared to more simple measurements as EAT and peri-coronary fat thickness and area. The quantity of EAT and peri-coronary fat is related with the presence of obesity and metabolic syndrome in patients suspected of CAD.