Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS). Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

Finding Needles in a Haystack: Using Geo-References to Enhance the Selection and Utilization of Landraces in Breeding for Climate-Resilient Cultivars of Upland Cotton (<i>Gossypium hirsutum</i> L.)

The genetic uniformity of cultivated cotton as a consequence of domestication and modern breeding makes it extremely vulnerable to abiotic challenges brought about by major climate shifts. To sustain productivity amidst worsening agro-environments, future breeding objectives need to seriously consider introducing new genetic variation from diverse resources into the current germplasm base of cotton. Landraces are genetically heterogeneous, population complexes that have been primarily selected for their adaptability to specific localized or regional environments. This makes them an invaluable genetic resource of novel allelic diversity that can be exploited to enhance the resilience of crops to marginal environments. The utilization of cotton landraces in breeding programs are constrained by the phenology of the plant and the lack of phenotypic information that can facilitate efficient selection of potential donor parents for breeding. In this review, the genetic value of cotton landraces and the major challenges in their utilization in breeding are discussed. Two strategies namely Focused Identification of Germplasm Strategy and Environmental Association Analysis that have been developed to effectively screen large germplasm collections for accessions with adaptive traits using geo-reference-based, mathematical modelling are highlighted. The potential applications of both approaches in mining available cotton landrace collections are also presented

Cell Membrane Features as Potential Breeding Targets to Improve Cold Germination Ability of Seeds

Cold stress breeding that focuses on the improvement of chilling tolerance at the germination stage is constrained by the complexities of the trait which involves integrated cellular, biochemical, hormonal and molecular responses. Biological membrane serves as the first line of plant defense under stress. Membranes receive cold stress signals and transduce them into intracellular responses. Low temperature stress, in particular, primarily and effectively affects the structure, composition and properties of cell membranes, which ultimately disturbs cellular homeostasis. Under cold stress, maintenance of membrane integrity through the alteration of membrane lipid composition is of prime importance to cope with the stress. This review describes the critical role of cell membranes in cold stress responses as well as the physiological and biochemical manifestations of cold stress in plants. The potential of cell membrane properties as breeding targets in developing strategies to improve cold germination ability is discussed using cotton (Gossypium hirsutum L.) as a model

Weathering the Cold: Modifying Membrane and Storage Fatty Acid Composition of Seeds to Improve Cold Germination Ability in Upland Cotton (Gossypium hirsutum L.)

Cotton is widely cultivated in temperate regions across the world and is often constrained by a short planting window that is bookended by low, suboptimal temperatures. With the growing interest in early season planting, improvements in the cold germination ability of cotton will be necessary to ensure the production stability of early planted crops. The importance of saturation levels of membrane and storage lipids in enhancing cold tolerance in plants, as well as improving cold germination ability in seeds have been widely researched in a range of plant species. While studies have shown that higher levels of unsaturated lipids can enhance cold germination ability and reduce seedling injury in other crops, similar efforts have been fairly limited in cotton. This review looks at the functional properties of membrane and storage lipids, and their role in membrane stability and reorganization during the early stages of germination. Additionally, the importance of storage lipid composition as an energy source to the growing embryo is described in the context of cellular energetics (i.e., fatty acid catabolism). Finally, perspectives in improving the cold germination of upland cotton by manipulating the fatty acid composition of both membrane and storage lipid content of seeds are presented

Genetic Analysis of an F₂ Population Derived from the Cotton Landrace Hopi Identified Novel Loci for Boll Glanding

Landraces are an important reservoir of genetic variation that can expand the narrow genetic base of cultivated cotton. In this study, quantitative trait loci (QTL) analysis was conducted using an F2 population developed from crosses between the landrace Hopi and inbred TM-1. A high-density genetic map spanning 2253.11 and 1932.21 cM for the A and D sub-genomes, respectively, with an average marker interval of 1.14 cM, was generated using the CottonSNP63K array. The linkage map showed a strong co-linearity with the physical map of cotton. A total of 21 QTLs were identified, controlling plant height (1), bract type (1), boll number (1), stem color (2), boll pitting (2), fuzz fiber development (2), boll shape (3), boll point (4), and boll glanding (5). In silico analysis of the novel QTLs for boll glanding identified a total of 13 candidate genes. Analysis of tissue-specific expression of the candidate genes suggests roles for the transcription factors bHLH1, MYB2, and ZF1 in gland formation. Comparative sequencing of open reading frames identified early stop codons in all three transcription factors in Hopi. Functional validation of these genes offers avenues to reduce glanding and, consequently, lower gossypol levels in cottonseeds without compromising the defense mechanisms of the plant against biotic stresses

Molecular Analysis of Oryza latifolia Desv. (CCDD Genome)-Derived Introgression Lines and Identification of Value-Added Traits for Rice (O. sativa L.) Improvement

Oryza latifolia\ua0is a tetraploid wild\ua0Oryza\ua0species with a CCDD genome that has been reported to harbor resistance to bacterial blight (BB), brown planthopper, and whitebacked planthopper. Aside from these traits,\ua0O. latifolia\ua0is also being tapped as a new source of resistance to lodging and high biomass production. To explore the genetic potential of\ua0O. latifolia\ua0as a novel genetic resource for the improvement of existing\ua0O. sativa\ua0cultivars, 27 disomic derivatives of\ua0O. latifolia\ua0monosomic alien addition lines (MAAL) were characterized for alien chromosome segment introgressions and evaluated for yield components, BB resistance, and strong stem characteristics. A total of 167 simple sequence repeat, sequence tagged site, and single nucleotide polymorphism markers, along with newly developed indel markers that were specifically designed to detect\ua0O. latifolia\ua0chromosome segment introgressions in an\ua0O. sativa\ua0background, were used to define alien introgressions in 27 disomics derived from\ua0O. latifolia\ua0MAALs. Genotype data showed that 32 unique introgressions spanning 0.31–22.73Mb were introgressed in different combinations in each of the 27 disomic derivatives. Evaluation of the disomic derivatives for agronomic traits identified lines with putative QTLs for resistance to Philippine races 3A, 4, 9A, and 9D of BB. Putative quantitative trait loci (QTLs) conferring strong stem in 19 out of the 27 disomic derivatives studied were also identified from\ua0O. latifolia\ua0introgressions on chromosome 6

Development of a PCR-based, genetic marker resource for the tomato-like nightshade relative, Solanum lycopersicoides using whole genome sequence analysis.

Solanum lycopersicoides is a wild nightshade relative of tomato with known resistance to a wide range of pests and pathogens, as well as tolerance to cold, drought and salt stress. To effectively utilize S. lycopersicoides as a genetic resource in breeding for tomato improvement, the underlying basis of observable traits in the species needs to be understood. Molecular markers are important tools that can unlock the genetic underpinnings of phenotypic variation in wild crop relatives. Unfortunately, DNA markers that are specific to S. lycopersicoides are limited in number, distribution and polymorphism rate. In this study, we developed a suite of S. lycopersicoides-specific SSR and indel markers by sequencing, building and analyzing a draft assembly of the wild nightshade genome. Mapping of a total of 1.45 Gb of S. lycopersicoides contigs against the tomato reference genome assembled a moderate number of contiguous reads into longer scaffolds. Interrogation of the obtained draft yielded SSR information for more than 55,000 loci in S. lycopersicoides for which more than 35,000 primers pairs were designed. Additionally, indel markers were developed based on sequence alignments between S. lycopersicoides and tomato. Synthesis and experimental validation of 345 primer sets resulted in the amplification of single and multilocus targets in S. lycopersicoides and polymorphic loci between S. lycopersicoides and tomato. Cross-species amplification of the 345 markers in tomato, eggplant, silverleaf nightshade and pepper resulted in varying degrees of transferability that ranged from 55 to 83%. The markers reported in this study significantly expands the genetic marker resource for S. lycopersicoides, as well as for related Solanum spp. for applications in genetics and breeding studies