Biology subjects

Davison, R.

Publications and source records attributed to Davison, R..

3 recordsLinked to original sources

bioRxiv2026

CMAS dampens anti-tumor immunity and associates with response to neoadjuvant immunotherapy in melanoma

Identifying immune-regulatory pathways to predict response is crucial for the efficacy of immune checkpoint blockade (ICB) immunotherapies. Sialylation is upregulated in tumor cells and modulates immune responses in cancer, yet its impact on patient clinical outcome and the spatial organization of the tumor microenvironment remain unclear. Here, using publicly available single-cell RNA sequencing data we show that expression of the sialylation master regulator CMAS in melanoma cells correlates with poorer patient survival. Using a murine melanoma model, we demonstrate that Cmas deletion in tumor cells severely impaired tumor growth and improved anti-tumor lymphoid and myeloid cell responses, increasing tumor cell-intrinsic susceptibility to interferon-gamma-, CD4+ T cell-, and macrophage-mediated killing. Single-cell spatial transcriptomics on neoadjuvant ICB-treated melanoma patient tumor biopsies revealed that CMAS expression in tumor cells inversely correlated with tumor cell proximity to and activation status of T cells and macrophages. Furthermore, expression of CMAS in tumor cells was increased in patients who did not respond to immunotherapy, compared to responders. Overall, our work identifies CMAS as a key modulator of tumor-immune dynamics associated with survival and response to neoadjuvant ICB immunotherapy in melanoma patients.

cancer biology↗

bioRxiv2020

Human uniqueness illustrated by life history diversity among small-scale societies and chimpanzees

BackgroundWe compare life histories and selection forces among chimpanzees and human subsistence societies in order to identify the age-specific vital rates that best explain fitness variation, selection pressures and species divergence. MethodsWe employ Life Table Response Experiments that quantify vital rate contributions to population growth rate differences. Although widespread in ecology, these methods have not been applied to human populations or to look at species differences among humans and chimpanzees. We also estimate correlations between vital rate elasticities and life history traits to investigate differences in selection pressures and test predictions of life history theory. ResultsChimpanzees earlier maturity and higher adult mortality drive species differences, whereas infant mortality and fertility variation drive differences among humans. Human fitness is decoupled from longevity by postreproductive survival, while chimpanzees forfeit higher potential lifetime fertility due to adult mortality attrition. Infant survival is often lower among humans, but lost fitness is recouped via short birth spacing and high peak fertility, thereby reducing selection on infant survival. Lastly, longevity and delayed maturity reduce selection on child survival, but among humans, recruitment selection is unexpectedly highest in longer-lived populations, which are also faster-growing due to high fertility. ConclusionHumans differ from chimpanzees more because of delayed maturity and adult mortality than child mortality or fertility rates. In both species, high child mortality reflects bet-hedging costs of quality/quantity tradeoffs borne by offspring, with high and variable child mortality likely regulating human population growth over evolutionary history. Among human subsistence societies, positive correlations between survival and natural fertility lead selection pressures in human subsistence societies to differ from modern populations undergoing demographic transition, due in part to positive correlations between longevity and natural fertility and negative correlations between recruitment elasticity and reproductive effort.

evolutionary biology↗

bioRxiv2020

Emergence of Lyme disease on treeless islands in Scotland, UK

Lyme disease (LD) is typically associated with forested habitats but has recently emerged on treeless islands in the Western Isles of Scotland. This has created a need to understand the environmental and human components of LD risk in open habitats. This study quantified both elements of LD risk and compared these between treeless islands with high and low LD incidence. We found high LD incidence was linked to higher prevalence in ticks (6.4% vs 0.4%) and increased human tick bite exposure. Most reported tick bites (72.7%) were within 1km of the home address and commonly in gardens. Residents on islands with high LD incidence reported increasing problems with ticks and suggested changing deer distribution as a potential driver. This study highlights the benefits to public health of an integrated approach to understand the factors contributing to LD emergence and a need to evaluate LD ecology in treeless habitats more broadly.

ecology↗