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At least 19 recordsLinked to original sources

bioRxiv2017

The 10,000 Immunomes Project: A resource for human immunology

New immunological assays now enable rich measurements of human immune function, but difficulty attaining enough measurements across sufficiently large and diverse cohorts has hindered describing normal human immune physiology on a large scale. Here we present the 10,000 Immunomes Project (10KIP), a diverse human immunology reference derived from over 44,000 individuals across 242 studies from ImmPort, a publicly available resource of raw immunology study data and protocols. We carefully curated datasets, aggregating subjects from healthy/control arms and harmonizing data across studies. We demonstrate 10KIPs utility by describing variations in serum cytokines and leukocytes by age, race, and sex; defining a baseline cell-cytokine network; and using 10KIP as a common control to describe immunologic changes in pregnancy. Subject-level data is available for interactive visualization and download at http://10kImmunomes.org/. We believe 10KIP can serve as a common control cohort and will accelerate hypothesis generation by clinical and basic immunologists across diverse populations.\n\nOne Sentence SummaryAn open online resource of human immunology data from more than 10,000 normal subjects including interactive data visualization and download enables a new look at immune system differences across age and sex, rapid hypothesis generation, and creation of custom control cohorts.

immunology↗

bioRxiv2018

Machine learning identifies the immunological signature of Juvenile Idiopathic Arthritis

Juvenile idiopathic arthritis (JIA) is the most common childhood rheumatic disease, with a strongly debated pathophysiological origin. Both adaptive and innate immune processes have been proposed as primary drivers, which may account for the observed clinical heterogeneity, but few high-depth studies have been performed. Here we profiled the adaptive immune system of 85 JIA patients and 43 age-matched controls, identifying immunological changes unique to JIA and others common across a broad spectrum of childhood inflammatory diseases. The JIA immune signature was shared between clinically distinct subsets, but was accentuated in the systemic JIA patients and those patients with active disease. Despite the extensive overlap in the immunological spectrum exhibited by healthy children and JIA patients, machine learning analysis of the dataset proved capable of diagnosis of JIA patients with ~90% accuracy. These results pave the way for large-scale longitudinal studies of JIA, where machine learning could be used to predict immune signatures that correspond to treatment response group.

immunology↗

bioRxiv2017

Immunological tolerance, pregnancy and pre-eclampsia: the roles of semen microbes and the father

Although it is widely recognised as involving two stages (poor placentation followed by oxidative stress/inflammation), the precise originating causes of pre-eclampsia (PE) remain elusive. We have previously brought together some of the considerable evidence that a (dormant) microbial component is commonly a significant part of its aetiology. However, apart from recognising, consistent with this view, that the many inflammatory markers of PE are also increased in infection, we had little to say about immunity, whether innate or adaptive. In addition, we focussed on the gut, oral and female urinary tract microbiomes as the main sources of the infection. We here marshall further evidence for an infectious component in PE, focussing on the immunological tolerance characteristic of pregnancy, and the well-established fact that increased exposure to the fathers semen assists this immunological tolerance. As well as these benefits, however, semen is not sterile, microbial tolerance mechanisms may exist, and we also review the evidence that semen may be responsible for inoculating the developing conceptus with microbes, not all of which are benign. It is suggested that when they are not, this may be a significant cause of preeclampsia. A variety of epidemiological and other evidence is entirely consistent with this, not least correlations between semen infection, infertility and PE. Our view also leads to a series of other, testable predictions. Overall, we argue for a significant paternal role in the development of PE through microbial infection of the mother via insemination. O_QD\"In one of the last articles which he wrote, the late Professor F J Browne (1958) expressed the opinion that all the essential facts about pregnancy toxaemia are now available and that all that is required to solve the problem is to fit them together in the right order, like the pieces of a jigsaw puzzle\" [1]\n\nC_QD O_QD\"It appears astonishing how little attention has been given in reproductive medicine to the maternal immune system over the last few decades.\" [2]\n\nC_QD

microbiology↗

bioRxiv2016

IRNdb: The database of immunologically relevant non-coding RNAs.

MicroRNAs (miRNAs), long non-coding RNAs (lncRNAs) and other functional non-coding RNAs (ncRNAs) have emerged as pivotal regulators involved in multiple biological processes. Recently, ncRNA control of gene expression has been identified as a critical regulatory mechanism in the immune system. Despite the great efforts made to discover and characterize ncRNAs, the functional role for most remains unknown. To facilitate discoveries in ncRNA regulation of immune system-related processes we developed the database of immunologically relevant ncRNAs and target genes (IRNdb). We integrated mouse data on predicted and experimentally supported ncRNA-target interactions, ncRNA and gene annotations, biological pathways and processes, and experimental data in a uniform format with a user-friendly web interface. The current version of IRNdb documents 12,930 experimentally supported miRNA-target interactions between 724 miRNAs and 2,427 immune-related murine targets. In addition, we recorded 22,453 lncRNA-immune target and 377 PIWI-interacting RNA-immune target interactions. IRNdb is a comprehensive searchable data repository which will be of help in studying the role of ncRNAs in the immune system.\n\nDatabase URL: http://irndb.org

Immunology↗

bioRxiv2017

Analysis of the immunological biomarker profile during acute Zika virus infection reveals the overexpression of CXCL10, a chemokine already linked to neuronal damage

Infection with Zika virus (ZIKV) manifests in a broad spectrum of disease ranging from mild illness to severe neurological complications. To define immunologic correlates of ZIKV infection, we characterized the levels of circulating cytokines, chemokines and growth factors in 54 infected patients of both genders, at five different time-points after symptoms onset using microbeads multiplex immunoassay; statistical analysis and data mining compared to 100 age-matched controls. ZIKV-infected patients present a striking systemic inflammatory response with high levels of pro-inflammatory mediators. Despite the strong inflammatory pattern, IL-1Ra and IL-4 are also induced during acute infection. Interestingly, the inflammatory cytokines, IL-1{beta}, IL-13, IL-17, TNF-, IFN-{gamma}; chemokines, CXCL8, CCL2, CCL5; and the growth factor G-CSF display a bimodal distribution accompanying viremia. While this is the first manuscript to document bimodal distributions of viremia in ZIKV infection, bimodal viremia has been documented in other viral infections with primary viremia peaks during mild systemic disease and a secondary viremia with distribution of the virus to organs and tissues. Moreover, biomarker network analysis demonstrated distinct dynamics in consonance with the bimodal viremia profiles at different time-points during ZIKV infection. Such robust cytokine and chemokine response has been associated with blood-brain barrier permeability and neuroinvasiveness in other flaviviral infections. High-dimensional data analysis further established CXCL10, a chemokine involved in fetal neuron apoptosis and Guillain-Barre syndrome, as the most promising biomarker of acute ZIKV infection for a potential clinical application.\n\nAuthor SummaryInfection with Zika virus manifests in a broad spectrum of disease ranging from mild illness to severe neurological complications. This study characterized the levels of circulating cytokines, chemokines and growth factors in Zika-infected patients showing an inflammatory immune response. Specifically, this study identified a chemokine, CXCL10, known to be involved in fetal neuron apoptosis and Guillain-Barre syndrome, as the most promising biomarker to characterize acute Zika virus infection.

immunology↗

bioRxiv2017

Immunologic Effect of Polysaccharides Extracted from Sipunculus nudus (SNP) on Hepatoma HepG2-bearing Mice

Since many studies have clarified the biological activity of polysaccharides, we investigated the effect of SNP which was the water-soluble polysaccharides extracted from Sipunculus nudus on Hepatoma HepG2-bearing Mice to verify the potential of SNP as an effective clinical agent for liver cancer therapy. SNP were administered at the doses of 50,100, and 200 mg/kg to HepG2-bearing mice to determine their antitumor effects. SNP had an inhibitory effect on the growth of HepG2 cells and enhanced the immunological effect on HepG2 tumor-bearing mice. SNP increased the expression of IL-2, IFN-{gamma}, and TNF- cytokines in serum, suggesting that SNP can strengthen the antitumor immune response. In addition, SNP increased ATF4, DDIT3, and IkB expression and decreased CYR61, HSP90, and VEGF expression, all of which are proteins involved in antitumor activity and cell death/survival. our results suggested that SNP may be a novel antitumor agent.\n\nSummary statementSNP(polysaccharides extracted from Sipunculus nudus) mediates anti-tumor activity through influencing immunoregulation, and SNP can be explored as a promising candidate for future anticancer drug.

cancer biology↗

bioRxiv2017

The interface of malignant and immunologic clonal dynamics in high-grade serous ovarian cancer

High-grade serous ovarian cancer exhibits extensive intratumoral heterogeneity coupled with widespread intraperitoneal disease. Despite this, metastatic spread of tumor clones is non-random, implying the existence of local microenvironmental factors that shape tumor progression. We interrogated the molecular interface between tumor-infiltrating lymphocytes (TIL) and cancer cells in 143 samples from 21 patients using whole-genome sequencing, immunohistochemistry, histologic image analysis, gene expression profiling, and T- and B-cell receptor sequencing. We identify 3 immunologic response categories, which frequently co-exist within individual patients. Furthermore, epithelial CD8+ TIL were inversely associated with malignant cell diversity, evidenced by subclonal neoepitope elimination and spatial tracking between tumor and T-cell clones. Intersecting mutational signatures and immune analysis showed that foldback inversion genomic aberrations lead to worse outcomes even in the presence of cytotoxic TIL (n=433). Thus, regional variation in immune contexture mirrors the pattern of intraperitoneal malignant spread, provoking new perspectives for treatment of this challenging disease.

cancer biology↗

bioRxiv2017

A Comprehensive Immunologic Portrait of Triple-Negative Breast Cancer

BackgroundTriple-negative breast cancer (TNBC) is a high-risk malignancy due to its high capacity for invasion and lack of targeted therapy. Immunotherapy continues to demonstrate efficacy in a variety of cancers, and thus may be a promising strategy for TNBC given the limited therapeutic options currently available for TNBC. In this study, we performed a comprehensive portrait of immunologic landscape of TNBC based on 2 large-scale breast cancer genomic data.\n\nMethodsWe compared expression levels of immune-related genes and gene-sets among TNBC, non-TNBC, and normal tissue, and within TNBCs of different genotypic or phenotypic features. Moreover, we explored the association of immune-related genes or gene-sets expression and survival prognosis in TNBC patients.\n\nResultsWe found that almost all analyzed immune-related gene-sets had significantly higher expression levels in TNBC than non-TNBC. These highly expressed gene-sets in TNBC included 15 immune cell type and function, human leukocyte antigen (HLA), cancer testis (CT), tumor-infiltrating lymphocytes (TILs), immune cell infiltrate, regulatory T (Treg) cells, immune checkpoint, cytokine and cytokine receptor, metastasis-promoting, pro-inflammatory and parainflammation (PI) gene-sets. Moreover, TP53-mutated, TNBC had significantly higher expression levels of the immune checkpoint, Treg, PI, and CT gene-sets, and lower expression levels of the immune cell infiltrate gene-set than TP53-wildtype TNBC. Furthermore, we found that elevated expression of most of the immune-related genes in TNBC was associated with the ER-status, while some were associated with both ER-and HER2-status. Elevated expression of the immune-related genes in TNBC was also associated with the high tumor mutation burden (TMB) in TNBC. Finally, elevated expression of the immune-related gene-sets was likely to be associated with better survival prognosis in TNBC.\n\nConclusionsOur findings suggest that TNBC is a breast cancer subtype with particularly strong immunogenicity, and therefore could be propitious to immunotherapeutic options.

cancer biology↗

bioRxiv2018

CytoBinning: immunological insights from multi-dimensional data

New cytometric techniques continue to push the boundaries of multi-parameter quantitative data acquisition at the single-cell level particularly in immunology and medicine. Sophisticated analysis methods for such ever higher dimensional datasets are rapidly emerging, with advanced data representations and dimensional reduction approaches. However, these are not yet standardized and clinical scientists and cell biologists are not yet experienced in their interpretation. More fundamentally their range of statistical validity is not yet fully established. We therefore propose a new method for the automated and unbiased analysis of high-dimensional single cell datasets that is simple and robust, with the goal of reducing this complex information into a familiar 2D scatter plot representation that is of immediate utility to a range of biomedical and clinical settings. Using publicly available flow cytometry and mass cytometry datasets we demonstrate that this method (termed CytoBinning), recapitulates the results of traditional manual cytometric analyses and leads to new and testable hypotheses.

bioinformatics↗

bioRxiv2018

Cytoskeletal tension actively sustains the T cell immunological synapse

When migratory T cells encounter antigen presenting cells (APCs), they arrest and form radially symmetric, stable intercellular junctions termed immunological synapses which facilitate exchange of crucial biochemical information and are critical for T cell immunity. While the cellular processes underlying synapse formation have been well-characterized, those that maintain the symmetry, and thereby the stability of the synapse remain unknown. Here we identify an antigen-triggered mechanism that actively promotes T cell synapse symmetry by generating cytoskeletal tension in the plane of the synapse through focal nucleation of actin via Wiskott -Aldrich syndrome Protein (WASP), and contraction of the resultant actin filaments by myosin II. Following T cell activation, WASP is degraded, leading to cytoskeletal rearrangement and tension decay, which result in synapse breaking. Thus, our study identifies and characterizes a mechanical program within otherwise highly motile T cells that sustains the symmetry and stability of the T cell-APC synaptic contact.

cell biology↗

bioRxiv2014

The immunologic V-gene repertoire in mammals

From recent whole genome shotgun data of 48 mammalian species, we have used our software VgenExtractor to obtain the functional V-gene sequence repertoire in order to conduct comparative phylogenetic studies. These studies reveal a large variation in the number of V-genes across mammalian species, ranging from a mere 36 V-genes in dolphins to nearly 600 V-genes in rats. Monotremes and marsupials are the only mammals possessing an additional locus, the TRMV, apart from the seven common loci found in mammals. Also, we show evidence for the loss of the light chain loci, specifically the V{kappa} chain in one microbat, and the V{lambda} chain in one rodent species. Finally, we suggest different features related to the evolution of immunoglobulin and T cell receptor loci, where frequent sequence duplications are seen in the former, while preserved and undiversified lineages are observed in the latter. All the V-gene sequences described in this study are available in the public database repository vgenerepertoire.org.

Immunology↗

bioRxiv2014

The whole diagram of the discovered host immunological pathways

Tfh initiates four eradicable immunities. Tfh includes FDC, LTi, IL21 CD4 T cell, and IgG/M B cell. Treg initiates four tolerable immunities. Treg includes DCreg, ILCreg, TGF{beta} CD4 T cell, and IgA B cell. TH1/TH1-like is immunity for intracellular bacteria/protozoa and type 4 delayed type hypersensitivity. TH1 includes M1 macrophage, mDC2, Tc1 CD8 T cell, IFNg CD4 T cell, ILC1, iNKT1, and IgG3 B cell. TH1-like includes M2 macrophage, ILC1, suppressive CD8 T cell, IFNg/TGF{beta} CD4 T cell, regulatory iNKT cells, and IgA1 B cell. TH2/TH9 is immunity for helminths and type1 IgE mediated hypersensitivity. TH2 includes iEOS eosinophil, Langerhans cell, basophil/MCt mast cell, IL-4 CD4 T cell, ILC2, iNKT2, and IgE/IgG4 B cell. TH9 includes rEOS eosinophil, basophils/mast cell MCct, IL-9 CD4 T cell, ILC2, regulatory iNKT cells, and IgA2 B cell. TH22/TH17 is immunity for extracellular bacteria/fungi and type 3 immune complex hypersensitivity. TH22 includes N1 neutrophils, mDC1, IL-22 CD4 T cell, ILC3(NCR+), iNKT17, and IgG2 B cell. TH17 includes N2 neutrophils, IL-17 CD4 T cell, regulatory iNKT cells, ILC3(NCR-), and IgA2 B cell. TH{beta}/TH3 is immunity for viruses and type 2 antibody dependent cytotoxic hypersensitivity. TH{beta} includes NK1 natural killer cell, pDC, Tc2 CD8 T cell, IL10 CD4 T cell, ILC10, iNKT10, and IgG1 B cell. TH3 includes NK2 natural killer cell, suppressive CD8 T cell, ILC10, IL-10/TGF{beta} CD4 T cell, regulatory iNKT cells, and IgA1 B cell. Summary sentenceThe summarized framework of host immunities to explain their relations to specific pathogens and hypersensitivities

Immunology↗

bioRxiv2016

Immunological Patterns from Four Melioidosis Cases: Constant and Variable Protein Antigens

Burkholderia pseudomallei is the causative agent of the melioidosis and is endemic to Southeast Asia and northern Australia. There is no available vaccine and accurate diagnosis is difficult, time-consuming and labor intensive. Early diagnosis is an important part of successful treatment and current serological tests are inadequate and based upon multiple antigens. Identifying specific immunogenic proteins which are highly seroreactive may yield potential diagnostic targets for detecting antibodies and antigens specific to melioidosis. We have used 2D gel electrophoresis and Western blotting analysis to analyze protein antigenicity of whole cell lysates extracted from four B. pseudomallei strains and the sera from the specific infected humans. We found a total of 135 immunogenic proteins, 62 of which we were able to identify to a specific gene by mass-spectrometry. Results from the Western blotting of each strains proteins and the corresponding patient serum reveal between 30 - 40% serum x strain specific immunogenic proteins. In most cases, these differences exist despite the fact that the genes encoding these proteins were present among all four B. pseudomallei strains. Eight particular proteins were immunogenic in all four strain x serum combinations and could represent novel diagnostic and vaccine subunit targets.

immunology↗

bioRxiv2016

Two-zone tumor tolerance can arise from a simple immunological feedforward motif that estimates tumor growth rates

Since the early 1990s, many authors have independently suggested that self/nonself recognition by the immune system might be modulated by the rates of change of antigen challenges. This paper introduces an extremely simple and purely conceptual mathematical model that allows dynamic discrimination of immune challenges. The main component of the model is a motif which is ubiquitous in systems biology, the incoherent feedforward loop, which endows the system with the capability to estimate exponential growth exponents, a prediction which is consistent with experimental work showing that exponentially increasing antigen stimulation is a determinant of immune reactivity. Combined with a bistable system and a simple feedback repression mechanism, an interesting phenomenon emerges as a tumor growth rate increases: elimination, tolerance (tumor growth), again elimination, and finally a second zone of tolerance (tumor escape). This prediction from our model is analogous to the \"two-zone tumor tolerance\" phenomenon experimentally validated since the mid 1970s. Moreover, we provide a plausible biological instantiation of our circuit using combinations of regulatory and effector T cells.

immunology↗

bioRxiv2017

c-Maf-dependent regulatory T cells mediate immunological tolerance to intestinal microbiota

Both microbial and host genetic factors contribute to the pathogenesis of autoimmune disease1-4. Accumulating evidence suggests that microbial species that potentiate chronic inflammation, as in inflammatory bowel disease (IBD), often also colonize healthy individuals. These microbes, including the Helicobacter species, have the propensity to induce autoreactive T cells and are collectively referred to as pathobionts4-8. However, an understanding of how such T cells are constrained in healthy individuals is lacking. Here we report that host tolerance to a potentially pathogenic bacterium, Helicobacter hepaticus (H. hepaticus), is mediated by induction of ROR{gamma}t+Foxp3+ regulatory T cells (iTreg) that selectively restrain pro-inflammatory TH17 cells and whose function is dependent on the transcription factor c-Maf. Whereas H. hepaticus colonization of wild-type mice promoted differentiation of ROR{gamma}t-expressing microbe-specific iTreg in the large intestine, in disease-susceptible IL-10-deficient animals there was instead expansion of colitogenic TH17 cells. Inactivation of c-Maf in the Treg compartment likewise impaired differentiation of bacteria-specific iTreg, resulting in accumulation of H. hepaticus-specific inflammatory TH17 cells and spontaneous colitis. In contrast, ROR{gamma}t inactivation in Treg only had a minor effect on bacterial-specific Treg-TH17 balance, and did not result in inflammation. Our results suggest that pathobiont-dependent IBD is a consequence of microbiota-reactive T cells that have escaped this c-Maf-dependent mechanism of iTreg-TH17 homeostasis.

immunology↗

bioRxiv2018

Effect of tributyltin chloride (TBT-Cl) exposure on expression of HSP90β1 in the river pufferfish (Takifugu obscurus): evidences for its immunologic function involving in exploring process

HSP90{beta}1 (known as GP96) is a vital endoplasmic reticulum depended chaperonin among the HSPs family. It plays important roles in regulating the growth, development, differentiation, and apoptosis of cells. Furthermore, it always processes and presents antigen of the tumor and keeps balance for the intracellular environment. In the present study, we explored the effect of tributyltin chloride (TBT-Cl) exposure on HSP90{beta}1 expression in river pufferfish, Takifugu obscurus. The full length of To-HSP90{beta}1 was gained with 2775 bp in length, an ORF obtained with 2412 bp encoding an 803 aa polypeptide. The phylogenetic tree was constructed and showed the close relationship to other fish species. The HSP90{beta}1 mRNA transcript was expressed in all tissues investigated. After the acute and chronic exposure of TBT-Cl, the mRNA level of To-HSP90{beta}1 significantly up-regulated in tissues of liver and gill. Moreover, the histochemistry study indicated the injury degree of TBT-Cl on liver and gill. Immunohistochemistry (IHC) staining results implied the cytoplasm reorganization after TBT-Cl stress and the function of immunoregulation for To-HSP90{beta}1. All the results indicated that HSP90{beta}1 may involve in the resistance to the invasion of TBT-Cl for keeping autoimmune homeostasis.

immunology↗

bioRxiv2018

Immunological characterization of a rat model of Duchenne’s disease and demonstration of improved muscle strength after anti-CD45RC antibody treatment

Duchenne muscular dystrophy (DMD) has as standard pharmacological therapy with corticoisteroids (CS) that decrease inflammation and immune responses present in patients and animal models. CS have however limited efficacy and important and numerous side effects. Therefore, there is a need for new anti-inflammatory and pro-tolerogenic treatments that could replace or decrease doses of CS. We first assessed the status of immune system of dystrophin-deficient rats (Dmdmdx) that closely reproduce the phenotype of DMD patients. Dmdmdx rats showed increased leukocyte infiltration in skeletal and cardiac muscles, containing mostly macrophages but also T cells, and increased expression of several cytokines. Anti-CD45RC Monoclonal antibody (Mab) treatment induced immune tolerance in models of organ transplantation and GVHD (Graft Versus Host Disease). We observed that muscles and blood of DMD patients contained T CD4+ and CD8+ expressing high levels of CD45RChigh cells. Treatment of young Dmdmdx rats with anti-CD45RC MAb corrected skeletal muscle strength associated to a depletion of effectors CD45RChigh T cells with no obvious side-effects. Prednisolone treatment of Dmdmdx rats similarly increased skeletal muscle strength and was also associated to a depletion of effectors CD45RChigh cells but resulted in severe weight loss.\n\nOverall, Dmdmdx rats display important immune inflammatory response and thus represent a useful model to analyze new anti-inflammatory and tolerogenic treatments for DMD. As an example, a new treatment with anti-CD45RC antibodies improved muscle strength in Dmdmdx rats as prednisolone did but without side effects. Anti-CD45RC therapy could complement other therapies in DMD patients.

immunology↗

bioRxiv2016

Tumor evolution of glioma intrinsic gene expression subtype associates with immunological changes in the microenvironment

SummaryWe leveraged IDH wild type glioblastomas and derivative neurospheres to define tumor-intrinsic transcription phenotypes. Transcriptomic multiplicity correlated with increased intratumoral heterogeneity and tumor microenvironment presence. In silico cell sorting demonstrated that M2 macrophages/microglia are the most frequent type of immune cells in the glioma microenvironment, followed by CD4 T lymphocytes and neutrophils. Hypermutation associated with CD8+ T cell enrichment. Longitudinal transcriptome analysis of 124 pairs of primary and recurrent gliomas showed expression subtype is retained in 53% of cases with no proneural to mesenchymal transition being apparent. Inference of the tumor microenvironment through gene signatures revealed a decrease in invading monocytes but a subtype dependent increase in M2 macrophages/microglia cells after disease recurrence. All expression datasets are accessible through http://recur.bioinfo.cnio.es/.\n\nSignificanceIDH wild type glioblastoma expression phenotypes have been related to tumor characteristics including genomic abnormalities and treatment response. We explored the intratumoral transcriptomic landscape, including a definition of tumor-intrinsic gene expression subtypes and how they relate to the different cellular components of the tumor immune environment. Comparison of matching primary and recurrent gliomas provided insights into the treatment-induced phenotypic tumor evolution. Proneural to mesenchymal transitions have long been suspected but were not apparent, while intratumoral heterogeneity was a predictor of subtype transition upon recurrence. Characterizing the evolving glioblastoma transcriptome en tumor microenvironment aids in designing more effective immunotherapy trials. Our study provides a comprehensive transcriptional and cellular landscape of IDH wild type GBM during treatment modulated tumor evolution.\n\nHighlightsO_LINext generation GBM-intrinsic transcriptional subtypes: proneural, classical, mesenchymal\nC_LIO_LIM2 macrophages, CD4+ T-lymphocytes and neutrophils dominate glioblastoma microenvironment\nC_LIO_LISensitivity to radiotherapy may associate with M2 macrophage presence\nC_LIO_LICD8+ T cells are enriched in hypermutated GBMs at diagnosis and recurrence\nC_LI

Preprint↗