Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches

Changes in demand for emergency ambulances during a nationwide lockdown that resulted in elimination of COVID-19: an observational study from New Zealand

Objective To examine the impact of a 5-week national lockdown on ambulance service demand during the COVID-19 pandemic in New Zealand.Design A descriptive cross-sectional, observational study.Setting High-quality data from ambulance electronic clinical records, New Zealand.Participants Ambulance records were obtained from 588 690 attendances during pre-lockdown (prior to 17 February 2020) and from 36 238 records during the lockdown period (23 March to 26 April 2020).Main outcome measures Ambulance service utilisation during lockdown was compared with pre-lockdown: (a) descriptive analyses of ambulance events and proportions of event types for each period, (b) absolute rates of ambulance attendance (event types/week) for each period.Results During lockdown, ambulance patients were more likely to be attended at home and less likely to be aged between 16 and 25 years. There was a significant increase in the proportion of lower acuity patients (Status 3 and Status 4) attended (p<0.001) and a corresponding increase in patients not transported from scene (p<0.001). Road traffic crashes (p<0.001) and alcohol-related incidents (p<0.001) significantly decreased. There was a decrease in the absolute number of weekly ambulance attendances (ratio (95% CI), 0.89 (0.87 to 0.91), p<0.001), attendances to respiratory conditions (0.74 (0.61 to 0.86), p=0.01), and trauma (0.81 (0.77 to 0.85), p<0.001). However, there was a significant increase in ambulance attendances for mental health conditions (1.37 (1.22 to 1.51), p=0.005).Conclusions Despite the relative absence of COVID-19 in the community during the 5-week nationwide lockdown, there were significant differences in ambulance utilisation during this period. The lockdown was associated with an increase in ambulance attendances for mental health conditions and is of concern. In considering future lockdowns, the potential implications on a population’s mental well-being will need to be seriously considered against the benefits of elimination of virus transmission