Biology subjects

Lupo, K.

Publications and source records attributed to Lupo, K..

4 recordsLinked to original sources

bioRxiv2025

PD-L1 ligation on NK cells induces a metabolic shift from glycolysis to fatty acid oxidation, enhancing tumor infiltration and control

PD-L1 blockade benefits even PD-L1-negative tumors, suggesting that non-tumor cells contribute to PD-L1 expression. Natural killer (NK) cells, vital mediators of innate immunity, vigorously express PD-L1 upon activation. We demonstrate that the ligation of PD-L1 on circulating and tumor-infiltrating NK cells with the therapeutic anti-PD-L1 antibody atezolizumab, soluble PD-1, or PD-1+ cells enhances NK cell-mediated tumor clearance via changes in metabolism, adhesion, and migration. PD-L1 engagement increases NK cell tumor infiltration via the CXCR3 pathway and cytoskeletal remodeling, supported by a metabolic shift from glycolysis to fatty acid oxidation (FAO). Loss of a key FAO enzyme, CPT1A, in NK cells abrogates the PD-L1-mediated anti-tumor effect, supporting a critical role for FAO in enhanced NK cell killing. The PD-L1-triggered shift away from glycolysis permits NK cells to remain highly effective at tumor killing in glucose-restricted TME. Taken together, PD-L1 ligation enhances NK cell cytotoxicity and tumor infiltration and contributes to NK resilience in challenging TME conditions, resulting in a more effective anti-tumor immunity. One sentence summaryPD-L1 engagement on NK cells enhances their tumor infiltration and cytotoxic activity by inducing a metabolic switch from glycolysis to fatty acid oxidation, enabling sustained function in the glucose-deprived tumor microenvironment.

immunology↗

bioRxiv2025

Pan-African metapopulation model explains Homo sapiens genetic and morphological evolution

A growing body of evidence has challenged the traditional assumption of a single-region origin for Homo sapiens, suggesting instead that our species originated from multiple geographically distinct populations in Africa, which intermittently exchanged genes and culture. However, our understanding of how this Pan-African metapopulation would have evolved through time is still limited. Furthermore, the drivers of such changes are uncertain, and quantitative models of the respective contributions of different African regions are lacking. Here we provide a complete reconstruction of the meta-population dynamics over the last 200,000 years by quantitatively integrating an ecological niche model, informed by archaeological sites, within a spatially explicit population genetic framework. The inferred metapopulation dynamics account for the divergence among all available contemporary and ancient genomes of African hunter-gatherers used to calibrate the model. In addition, it also accurately predicts the patterns of craniometric diversification across the continent from the Late Middle Pleistocene to the present. Finally, we show how the climate-driven changes in population sizes and connectivity are congruent with major patterns of archaeological and phenotypic diversification over the last 200,000 years across the African continent.

evolutionary biology↗

bioRxiv2021

Population inter-connectivity over the past 120,000 years explains distribution and diversity of Central African hunter-gatherers

The evolutionary history of African hunter-gatherers holds key insights into modern human diversity. Here we combine ethnographic and genetic data on Central African hunter-gatherers (CAHG) to show that their current distribution and density is explained by ecology rather than by a displacement to marginal habitats due to recent farming expansions, as commonly assumed. We also predict hunter-gatherer presence across Central Africa over the past 120,000 years using paleoclimatic reconstructions, which were statistically validated by dated archaeological sites. Finally, we show that genomic estimates of separation times between CAHG groups match our ecological estimates of periods favouring population splits, and that recoveries of connectivity would have facilitated subsequent gene-flow. Our results reveal that CAHG stem from a deep history of partially connected populations. This form of sociality allowed the coexistence of relatively large effective population sizes and local differentiation, with important implications for the evolution of genetic and cultural diversity in Homo sapiens.

evolutionary biology↗

bioRxiv2019

The Life History of Human Foraging: Cross-Cultural and Individual Variation

Human adaptation depends upon the integration of slow life history, complex production skills, and extensive sociality. Refining and testing models of the evolution of human life history and cultural learning will benefit from increasingly accurate measurement of knowledge, skills, and rates of production with age. We pursue this goal by inferring individual hunters of hunting skill gain and loss from approximately 23,000 hunting records generated by more than 1,800 individuals at 40 locations. The model provides an improved picture of ages of peak productivity as well as variation within and among ages. The data reveal an average age of peak productivity between 30 and 35 years of age, though high skill is maintained throughout much of adulthood. In addition, there is substantial variation both among individuals and sites. Within study sites, variation among individuals depends more upon heterogeneity in rates of decline than in rates of increase. This analysis sharpens questions about the co-evolution of human life history and cultural adaptation. It also demonstrates new statistical algorithms and models that expand the potential inferences drawn from detailed quantitative data collected in the field.

animal behavior and cognition↗