SummaryImmune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens.Video Abstract

Feedback with soil biota is an important determinant of terrestrial plant diversity. However, the factors regulating plant-soil feedback, which varies from positive to negative among plant species, remain uncertain. In a large-scale study involving 55 species and 550 populations of North American trees, the type of mycorrhizal association explained much of the variation in plant-soil feedbacks. In soil collected beneath conspecifics, arbuscular mycorrhizal trees experienced negative feedback, whereas ectomycorrhizal trees displayed positive feedback. Additionally, arbuscular mycorrhizal trees exhibited strong conspecific inhibition at multiple spatial scales, whereas ectomycorrhizal trees exhibited conspecific facilitation locally and less severe conspecific inhibition regionally. These results suggest that mycorrhizal type, through effects on plant-soil feedbacks, could be an important contributor to population regulation and community structure in temperate forests.

One Sentence Summary: Empirical evidence from grasslands around the world demonstrates a humped-back relationship between plant species richness and biomass at the 1 m 2 plot scale.Abstract: One of the central problems of ecology is the prediction of species diversity. The humped-back model (HBM) suggests that plant diversity is highest at intermediate levels of productivity; at low productivity few species can tolerate the environmental stresses and at high productivity a small number of highly competitive species dominate. A recent study claims to have comprehensively refuted the HBM. Here we show, using the largest, most geographically diverse dataset ever compiled and specifically built for testing this model that if the conditions are met, namely a wide range in biomass at the 1 m 2 plot level and the inclusion of plant litter, the relationship between plant biomass and species richness is hump shaped, supporting the HBM. Our findings shed new light on the prediction of plant diversity in grasslands, which is crucial for supporting management practices for effective conservation of biodiversity. 4Main Text: The relationship between plant diversity and productivity is a topic of intense debate (1-6). The HBM states that plant species richness peaks at intermediate productivity, taking above-ground biomass as a proxy for annual net primary productivity (ANPP) (7-9). This diversity peak is driven by two opposing processes; in unproductive and disturbed ecosystems where there is low plant biomass, species richness is limited by either stress, such as insufficient water and mineral nutrients, or high levels of disturbance-induced removal of biomass, which few species are able to tolerate. In contrast, in the low disturbance and productive conditions that generate high plant biomass it is competitive exclusion by a small number of highly competitive species that is hypothesized to constrain species richness (7-9). Other mechanisms proposed to explain the unimodal relationship between species richness and productivity include disturbance (10), evolutionary history and dispersal limitation (11,12), and density limitation affected by plant size (13).Different case studies have supported or rejected the HBM, and three separate meta-analyses reached different conclusions (14). This inconsistency may indicate a lack of generality of the HBM, or it may reflect a sensitivity to study characteristics including the type(s) of plant communities considered, the taxonomic scope, the length of the gradient sampled, the spatial grain and extent of analyses (14,15), and the particular measure of net primary productivity (16). Although others would argue (6), we maintain that the question remains whether the HBM serves as a useful and general model for grassland ecosystem theory and management. 5 We quantified the form and strength of the richness-productivity relationship using novel data from a globally-coordinated (17), distributed, scale-standardized and consistently designed survey, in which plant richness and biomass were m...

SummaryCD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology.