Iron boosts anti-tumor type 1 T-cell responses and anti-PD1 immunotherapy.

Cancers only develop if they escape immunosurveillance, and the success of cancer immunotherapies relies in most cases on their ability to restore effector T-cell functions, particularly IFN-γ production. Revolutionizing the treatment of many cancers, immunotherapies targeting immune checkpoints such as PD1 can increase survival and cure patients. Unfortunately, although immunotherapy has greatly improved the prognosis of patients, not all respond to anti-PD1 immunotherapy, making it crucial to identify alternative treatments that could be combined with current immunotherapies to improve their effectiveness. Here, we show that iron supplementation significantly boosts T-cell responses in vivo and in vitro. This boost is associated with a metabolic reprogramming of T cells in favor of lipid oxidation. We also found that the "adjuvant" effect of iron led to a marked slowdown of tumor-cell growth after tumor-cell line transplantation in mice. Specifically, our results suggest that iron supplementation promotes anti-tumor responses by increasing IFN-γ production by T cells. In addition, iron supplementation considerably improves the efficacy of anti-PD1 cancer immunotherapy in mice. Finally, our study suggests that, in cancer patients, the quality and efficacy of the anti-tumor response following anti-PD1 immunotherapy may be modulated by plasma ferritin levels. In summary, our results suggest the benefits of iron supplementation on the reactivation of anti-tumor responses and support the relevance of a fruitful association between immunotherapy and iron supplementation.

Highly pathogenic avian influenza affects vultures' movements and breeding output.

An exceptional highly pathogenic avian influenza (HPAI) outbreak due to H5N1 virus genotypes belonging to clade 2.3.4.4.b has been affecting birds worldwide since autumn 2021.1,2,3 Mortality caused by viral infection has been well documented in poultry and more recently in wild birds, especially in seabird-breeding colonies.4,5,6 However, there is a critical lack of knowledge about how terrestrial birds deal with HPAI virus infections in terms of behavior and space use, especially during the breeding season.7,8,9 Understanding how birds move when they are infected could help evaluate the risk of spreading the virus at a distance among other populations of wild or domestic birds, this latter risk being especially important for commensal bird species. Through long-term GPS tracking, we described the changes in daily movement patterns of 31 adult griffon vultures Gyps fulvus in two French sites in 2022 compared with 3 previous years. In spring 2022, 21 vultures at both sites showed periods of immobility at the nest, during 5.6 days on average. Positive serological status of 2 individuals confirmed that they had been infected by HPAI viruses. Death was recorded for 3 of the 31 tracked individuals, whereas all others recovered and returned quickly to their foraging routine, although at least 9 birds failed breeding. Such immobility patterns and death rates were never observed in previous years and were not related to weather conditions. The high immobility behavior of infected birds could reduce the risks of transmission. The observed vulnerability to HPAI viruses questions the resistance of endangered vulture species worldwide if infected.

Differential survival throughout the full annual cycle of a migratory bird presents a life-history trade-off.

Long-distance migrations are among the most physically demanding feats animals perform. Understanding the potential costs and benefits of such behaviour is a fundamental question in ecology and evolution. A hypothetical cost of migration should be outweighed by higher productivity and/or higher annual survival, but few studies on migratory species have been able to directly quantify patterns of survival throughout the full annual cycle and across the majority of a species' range. Here, we use telemetry data from 220 migratory Egyptian vultures Neophron percnopterus, tracked for 3,186 bird months and across approximately 70% of the species' global distribution, to test for differences in survival throughout the annual cycle. We estimated monthly survival probability relative to migration and latitude using a multi-event capture-recapture model in a Bayesian framework that accounted for age, origin, subpopulation and the uncertainty of classifying fates from tracking data. We found lower survival during migration compared to stationary periods (ß = -0.816; 95% credible interval: -1.290 to -0.318) and higher survival on non-breeding grounds at southern latitudes (<25°N; ß = 0.664; 0.076-1.319) compared to on breeding grounds. Survival was also higher for individuals originating from Western Europe (ß = 0.664; 0.110-1.330) as compared to further east in Europe and Asia, and improved with age (ß = 0.030; 0.020-0.042). Anthropogenic mortalities accounted for half of the mortalities with a known cause and occurred mainly in northern latitudes. Many juveniles drowned in the Mediterranean Sea on their first autumn migration while there were few confirmed mortalities in the Sahara Desert, indicating that migration barriers are likely species-specific. Our study advances the understanding of important fitness trade-offs associated with long-distance migration. We conclude that there is lower survival associated with migration, but that this may be offset by higher non-breeding survival at lower latitudes. We found more human-caused mortality farther north, and suggest that increasing anthropogenic mortality could disrupt the delicate migration trade-off balance. Research to investigate further potential benefits of migration (e.g. differential productivity across latitudes) could clarify how migration evolved and how migrants may persist in a rapidly changing world.