Biology subjects

Neophytou, C.

Publications and source records attributed to Neophytou, C..

3 recordsLinked to original sources

bioRxiv2026

Endothelin receptor blockade potentiates adoptive T cell and CAR T cell therapies

Adoptive T cell therapies have transformed the treatment of selected haematological malignancies but remain limited in many cancer settings by biological barriers that restrict effective and durable antitumour responses. Here, we investigated whether pharmacological blockade of the endothelin receptor pathway, which regulates vascular, stromal and immune processes relevant to antitumour responses, could enhance T cell-based cellular immunotherapy. Using orthotopic 4T1 triple-negative breast cancer and A20 B cell lymphoma models, we evaluated endothelin receptor blockade with non-engineered adoptive T cell therapy and anti-CD19 CAR T cell therapy, respectively, with or without immune checkpoint inhibition. Endothelin receptor blockade substantially increased objective responses across both therapeutic platforms, while the addition of immune checkpoint inhibition further increased response frequency and promoted maintained complete responses, resulting in the most durable tumour control. Mice achieving maintained complete responses resisted tumour rechallenge, consistent with long-term antitumour immune protection. High-dimensional T cell profiling identified distinct intratumoral T cell states associated with tumour control and elevated CD2 expression as a recurring feature across these populations. Together, these findings identify endothelin receptor blockade as a rational combinatorial strategy for enhancing T cell-based cellular immunotherapy and provide a strong rationale for the clinical evaluation of this therapeutic strategy.

immunology↗

bioRxiv2026

Adaptive variation in drought-related traits across southern and central European white oak (Quercus sect. Quercus) populations

European white oaks grow from the Mediterranean coast to Southern Scandinavia, a huge environmental gradient that has likely fostered environmental adaptation. In the face of climate change, leveraging adaptations through assisted gene flow could help improve drought tolerance and maintain forest health, but requires an understanding of the species-specific patterns of adaptation to be successful at the target location. In this study, three common gardens were established in Switzerland, Tuerkiye, and Austria for two European white oak species (Quercus robur, and Q. pubescens) using provenances from Central and Southern Europe. Almost 900 oak seedlings were measured at key water-use efficiency and life history traits for their first two year of life and genotyped with low coverage whole-genome sequencing. Trait heritability and environmental adaptation were then explored through pedigree-free animal models, while the genomic architecture of traits was mapped using a genome wide association study ("GWAS"). Across the species, the heritability of measured traits was moderate to high, but common garden had a strong impact, signalling an environmental effect on the phenotype. Adaptation to precipitation seasonality was detected in key productivity and growth traits for both species, but had a small effect on absolute trait values. The GWAS identified a striking 150 kbp association in the Cyclic Nucleotide-Gated Ion Channel gene family with leaf d13C values. This gene family is involved in stomata opening and likely impacts the intrinsic water use efficiency under stress. Together, the strong signals of phenotypic plasticity and rather weak signals of climatic adaptation in seedlings suggest that assisted gene flow in these two white oaks is relevant only for highly drought-sensitive populations, if conducted managers should focus on seeds sources with high precipitation seasonality and smaller leaf sizes.

evolutionary biology↗

bioRxiv2023

Conserving genetic diversity during climate change:Niche marginality and discrepant monitoring capacity in Europe

Genetic monitoring of populations currently attracts interest in the context of the Convention on Biological Diversity but needs long-term planning and investments. Genetic diversity has been largely neglected in biodiversity monitoring, and when addressed is treated separately, detached from other conservation issues, such as habitat alteration due to climate change. Genetic monitoring supports the conservation and management of fisheries, game, and threatened populations. It also can contribute to the assessment of predicted and realized impacts of climate change, and their management. We report the first accounting of genetic monitoring efforts among countries in Europe (their genetic monitoring capacity, GMC) to determine where GMC suggests the combination of national infrastructure, political support and resources for continued and expanded monitoring. Overlaying GMC with areas where species ranges approach current and future climate niche limits (i.e., niche marginality) helps identify whether GMC coincides with anticipated climate change effects on biodiversity. Our analysis suggests that country area extent, financial resources, and conservation policy influence GMC, high values of which inconsistently match joint species patterns of climate niche marginality. Populations at niche margins likely hold genetic diversity that is important to adaptation to changing climate, and our results illuminate the need in Europe for expanded genetic monitoring across the climate gradients occupied by species, a need arguably greatest in southeastern European countries.

ecology↗