Biology subjects

He, B.

Publications and source records attributed to He, B..

At least 73 records · Page 4Linked to original sources

bioRxiv2024

Mitochondrial uncoupler and retinoic acid synergistically induce differentiation and inhibit proliferation in neuroblastoma

Neuroblastoma is a leading cause of death in childhood cancer cases. Unlike adult malignancies, which typically develop from aged cells through accumulated damage and mutagenesis, neuroblastoma originates from neural crest cells with disrupted differentiation. This distinct feature provides novel therapeutic opportunities beyond conventional cytotoxic methods. Previously, we reported that the mitochondrial uncoupler NEN (niclosamide ethanolamine) activated mitochondria respiration to reprogram the epigenome, promoting neuronal differentiation. In the current study, we further combine NEN with retinoic acid (RA) to promote neural differentiation both in vitro and in vivo. The treatment increased the expression of RA signaling and neuron differentiation-related genes, resulting in a global shift in the transcriptome towards a more favorable prognosis. Overall, these results suggest that the combination of a mitochondrial uncoupler and the differentiation agent RA is a promising therapeutic strategy for neuroblastoma.

cancer biology↗

bioRxiv2024

Transcranial Focused Ultrasound Remotely Modulates Extrastriate Visual Cortex with Subregion Specificity

Low-intensity transcranial focused ultrasound (tFUS) has emerged as a powerful neuromodulation tool characterized by its deep penetration and precise spatial targeting to influence neural activity. Our study directed low-intensity tFUS stimulation onto a region of prefrontal cortex (the frontal eye field, or FEF) of a rhesus macaque to examine its impact on a remote site, the extrastriate visual cortex (area V4). This pair of cortical regions form a top-down modulatory circuit that has been studied extensively with electrical microstimulation. To measure the impact of tFUS stimulation, we recorded local field potentials (LFPs) and multi-unit spiking activities from a multi-electrode array implanted in the visual cortex. To deliver tFUS stimulation, we leveraged a customized 128-element random array ultrasound transducer with improved spatial targeting. We observed that tFUS stimulation in FEF produced modulation of V4 neuronal activity, either through enhancement or suppression, dependent on the pulse repetition frequency of the tFUS stimulation. Electronically steering the transcranial ultrasound focus through the targeted FEF cortical region produced changes in the level of modulation, indicating that the tFUS stimulation was spatially targeted within FEF. Modulation of V4 activity was confined to specific frequency bands, and this modulation was dependent on the presence or absence of a visual stimulus during tFUS stimulation. A control study targeting the insula produced no effect, emphasizing the region-specific nature of tFUS neuromodulation. Our findings shed light on the capacity of tFUS to modulate specific neural pathways and provide a comprehensive understanding of its potential applications for neuromodulation within brain networks.

neuroscience↗

bioRxiv2024

A split crRNA with CRISPR-Cas12a enables highly sensitive, selective, and multiplexed detection of RNA and DNA

The complete 40-nt CRISPR RNA (crRNA) of Cas12a can be artificially divided into two parts, including the 20-nt scaffold RNA with fixed sequences and the 20-nt spacer RNA with variable sequences, respectively. Herein, we found that Cas12a protein, scaffold RNA, and spacer RNA can be reassembled into an active ribonucleoprotein (RNP) which has a trans-cleavage activity comparable to that of wild-type Cas12a RNP. By leveraging such split CRISPR-Cas12a system (SCas12a), we devised fast fluorescence and lateral flow assays for highly sensitive, selective, and multiplexed detection of miRNAs without the need for reverse transcription and pre-amplification, achieving a limit of detection (LoD) of 10 fM. Additionally, our SCas12a assay enables detecting long-stranded RNA without secondary structure, as well as distinguishing mature miRNA from its precursor (pre-miRNA) that comprises the same sequence of miRNA. Beyond RNA detection, SCas12a outperforms wild-type Cas12a in specificity towards DNA point mutations. In combination with recombinase polymerase amplification (RPA), we set up a one-pot assay to detect attomolar concentrations of human papillomavirus (HPV) in patient samples. In conclusion, this work provides a simple, cost-effective, yet powerful SCas12a-based rapid nucleic acid detection platform in various diagnostic settings. Significance StatementConventional Cas12a-based diagnostic methods cannot directly detect RNA targets. Here, we develop rapid fluorescence and lateral flow assays based on a split Cas12a system (called SCas12a), achieving amplification-free detection of RNA with high sensitivity and specificity. By supplying pooled activators, our method enables multiplexed detection of miRNA and DNA targets. In addition, SCas12a can discriminate mature miRNA from its pre-miRNA, which was achieved for the first time with CRISPR detection technology. Moreover, SCas12a outperforms wild-type Cas12a in specificity towards point mutation and can be combined with RPA to detect attomolar concentration of HPV in patient samples. Overall, this work offers a generic "split crRNA-activator" strategy for developing new CRISPR diagnostic tools.

biochemistry↗

bioRxiv2023

CLAIR: An integrated lipid database across multiple crop species

Oilseed crops, which are rich in plant lipids, provide essential fatty acids for human consumption and serve as major sources of biofuels and essential raw materials for the chemical industry. As a result of population growth and ecological changes, the demand for vegetable oil is increasingly outpacing supply. A comprehensive understanding of the genes involved in lipid metabolism in oilseed crops and the regulatory relationships among these genes is essential for improving oil content. However, current studies on lipid metabolism genes rely heavily on a decade-old database of genes involved in lipid metabolism in Arabidopsis thaliana. To address this issue, we mined the literature, integrated data from various databases and studies, and aligned homologs of lipid metabolism genes from nine oilseed crops to construct a comprehensive set of lipid metabolism genes in plants. Using this approach, we identified 221 additional lipid metabolism genes. In addition, we created a user-friendly lipid database called CLAIR (Crop Lipid-Associated Information Resource) by integrating and mining multi-omics data from nine major oil crops. The database is available at http://www.clipair.cn/. These resources should facilitate further research and exploration of lipid metabolism in oil crops, ultimately contributing to improved oil production.

plant biology↗

bioRxiv2023

De novo generation of T-cell receptors with desired epitope-binding property by leveraging a pre-trained large language model

Generating T-cell receptors (TCRs) with desired epitope-binding properties is a fundamental step in the development of immunotherapies, yet heavily relies on laborious and expensive wet experiments. Recent advancements in generative artificial intelligence have demonstrated promising power in protein design and engineering. In this regard, we propose a large language model, termed Epitope-Receptor-Transformer (ERTransformer), for the de novo generation of TCRs with the desired epitope-binding property. ERTransformer is built on EpitopeBERT and ReceptorBERT, which are trained using 1.9 million epitope sequences and 33.1 million TCR sequences, respectively. To demonstrate the model capability, we generate 1000 TCRs for each of the five epitopes with known natural TCRs. The artificial TCRs exhibit low sequence identity (average Bit-score 27.64 with a standard deviation of 1.50) but high biological function similarity (average BLOSUM62 score 32.32 with a standard deviation of 12.01) to natural TCRs. Furthermore, the artificial TCRs are not very structurally identical to natural ones (average RMSD 2.84 [A] with a standard deviation of 1.21 [A]) but exhibit a comparable binding affinity towards the corresponding epitopes. Our work highlights the tremendous potential of applying ERTransformer to generate novel TCRs with desired epitope-binding ability.

bioinformatics↗

bioRxiv2023

De novo generation of antibody CDRH3 with a pre-trained generative large language model

Artificial Intelligence (AI) techniques have made great advances in assisting antibody design. However, antibody design still heavily relies on isolating antigen-specific antibodies from serum, which is a resource-intensive and time-consuming process. To address this issue, we propose a Pre-trained Antibody generative large Language Model (PALM) for the de novo generation of artificial antibodies heavy chain complementarity-determining region 3 (CDRH3) with desired antigen-binding specificity, reducing the reliance on natural antibodies. We also build a high-precision model antigen-antibody binder (A2binder) that pairs antigen epitope sequences with antibody sequences to predict binding specificity and affinity. PALM-generated antibodies exhibit binding ability to SARS-CoV-2 antigens, including the emerging XBB variant, as confirmed through in-silico analysis and in-vitro assays. The in-vitro assays validated that PALM-generated antibodies achieve high binding affinity and potent neutralization capability against both wild-type and XBB spike proteins of SARS-CoV-2. Meanwhile, A2binder demonstrated exceptional predictive performance on binding specificity for various epitopes and variants. Furthermore, by incorporating the attention mechanism into the PALM model, we have improved its interpretability, providing crucial insights into the fundamental principles of antibody design.

bioinformatics↗

bioRxiv2023

Continuous Tracking using Deep Learning-based Decoding for Non-invasive Brain-Computer Interface

Brain-computer interfaces (BCI) using electroencephalography (EEG) provide a non-invasive method for users to interact with external devices without the need for muscle activation. While noninvasive BCIs have the potential to improve the quality of lives of healthy and motor impaired individuals, they currently have limited applications due to inconsistent performance and low degrees of freedom. In this study, we use deep learning (DL)-based decoders for online Continuous Pursuit (CP), a complex BCI task requiring the user to track an object in two-dimensional space. We developed a labeling system to use CP data for supervised learning, trained DL-based decoders based on two architectures, including a newly proposed adaptation of the PointNet architecture, and evaluated the performance over several online sessions. We rigorously evaluated the DL-based decoders in a total of 28 human participants, and found that the DL-based models improved throughout the sessions as more training data became available and significantly outperformed a traditional BCI decoder by the last session. We also performed additional experiments to test an implementation of transfer learning by pre-training models on data from other subjects, and mid-session training to reduce inter-session variability. The results from these experiments showed that pre-training did not significantly improve performance, but updating the models mid-session may have some benefit. Overall, these findings support the use of DL-based decoders for improving BCI performance in complex tasks like CP, which can expand the potential applications of BCI devices and help improve the quality of lives of healthy and motor-impaired individuals. Significance StatementBrain-computer Interfaces (BCI) have the potential to replace or restore motor functions for patients and can benefit the general population by providing a direct link of the brain with robotics or other devices. In this work, we developed a paradigm using deep learning (DL)-based decoders for continuous control of a BCI system and demonstrated its capabilities through extensive online experiments. We also investigate how DL performance is affected by varying amounts of training data and collected more than 150 hours of BCI data that can be used to train new models. The results of this study provide valuable information for developing future DL-based BCI decoders which can improve performance and help bring BCIs closer to practical applications and wide-spread use.

bioengineering↗

bioRxiv2023

Beta-catenin inhibition disrupts the homeostasis of osteogenic/adipogenic differentiation leading to the development of glucocorticoid-induced osteonecrosis of femoral head

Glucocorticoid-induced osteonecrosis of the femoral head (GONFH) is a common refractory joint disease characterized by bone damage and the collapse of femoral head structure. However, the exact pathological mechanisms of GONFH remain unknown. Here, we observed abnormal osteogenesis and adipogenesis associated with decreased {beta}-catenin in the necrotic femoral head of GONFH patients. In vivo and in vitro studies further revealed that glucocorticoid exposure disrupted osteogenic/adipogenic differentiation of bone marrow mesenchymal cells (BMSCs) by inhibiting {beta}-catenin signaling in glucocorticoid-induced GONFH rats. Col2+ lineage largely contributes to BMSCs, and was found an osteogenic commitment in the femoral head through 9 months of lineage trace. Specific deletion of {beta}-catenin in Col2+ cells shifted their commitment from osteoblasts to adipocytes, leading to a full spectrum of disease phenotype of GONFH in adult mice. Overall, we uncover that {beta}-catenin inhibition disrupting the homeostasis of osteogenic/adipogenic differentiation contributes to the development of GONFH, and identify an ideal genetic modified mouse model of GONFH.

pathology↗

bioRxiv2023

Transcranial Focused Ultrasound to V5 Enhances Human Visual Motion Brain-Computer Interface by Modulating Feature-Based Attention

Paralysis affects roughly 1 in 50 Americans. While there is no cure for the condition, brain-computer interfaces (BCI) can allow users to control a device with their mind, bypassing the paralyzed region. Non-invasive BCIs still have high error rates, which is hypothesized to be reduced with concurrent targeted neuromodulation. This study examines whether transcranial focused ultrasound (tFUS) modulation can improve BCI outcomes, and what the underlying mechanism of action might be through high-density electroencephalography (EEG)-based source imaging (ESI) analyses. V5-targeted tFUS significantly reduced the error for the BCI speller task. ESI analyses showed significantly increased theta activity in the tFUS condition at both V5 and downstream the dorsal visual processing pathway. Correlation analysis indicates that the dorsal processing pathway connection was preserved during tFUS stimulation, whereas extraneous connections were severed. These results suggest that V5-targeted tFUS mechanism of action is to raise the brains feature-based attention to visual motion.

neuroscience↗

bioRxiv2023

The longitudinal single-cell panorama of cynomolgus monkey ovary throughout lifespan revealed a conserved ovarian clock between primates

Ovarian function is critical for female fertility and impacts reproductive longevity. It is of great importance to accurately predict the aging process within the ovary for fertility assessment and disease diagnosis. However, cell metrics for evaluating the ovarian aging rate are still in urgent need, and molecular insights into ovarian development and dysfunction during the primate life course are also limited. Here, we reported large-scale ovarian cell atlas of consecutive development of cynomolgus monkeys across 22 years with 20 time points, covering the foetal, newborn, prepubertal, pubertal, adult, perimenopausal and menopausal stages. We characterized and validated distinct molecular signatures of each cluster of cells within primate ovaries, and uncovered a previously undocumented RHOXF1-positive oocyte type during primordial follicle assembly in primates. Furthermore, the constitution and developmental trajectories of primate germ cells, granulosa cells and stromal / theca cells were also elucidated, and their precursors were identified. More importantly, dynamics of cellular compositions were unravelled through the ovarian development, featured by granulosa, epithelial, stromal, and immune cells that showed strong temporal heterogeneity spanning lifetime, whilst referred to the key function during the corresponding stages. Based on the correlations of each cell type with age and stage-specific molecular dynamics, we further constructed a transcriptomic ovarian clock which could perceive an effective biological age prediction of the ovary and further applied to humans. The findings reveal granulosa, epithelial, and stromal cells as the highest performance predictors of ovarian biological age, while highlighting the crucial role of AGE-RAGE and Relaxin signaling pathways in regulating ovarian aging. Our work not only provide valuable resource for obtaining insights into the development, aging and dysfunction of key organs, but also establish a transcriptomic clock to predict biological ovarian aging thus to be potential clinical implementation in future.

developmental biology↗

bioRxiv2023

Detection and characterization of a novel bat filovirus (Dehong virus, DEHV) in fruit bats

Although bats are natural hosts of most filoviruses (FiVs), with the pathogenic ones frequently causing deadly haemorrhagic fevers in Africa, the viruses are difficult to trace. Recently, multiple divergent FiVs have been uncovered in China, raising concerns about their threat to public health. Here we report the detection of bat-borne FiVs at the interface of orchards between bats and humans, eventually resulting in the discovery of a novel FiV, Dehong virus (DEHV), from Rousettus leschenaultii (R. leschenaultii) bats. DEHV has the largest genome, and the phylogeny places it between the genera Dianlovirus and Marburgvirus, suggesting its classification as a prototype of a new genus within the family Filoviridae. Our study emphasizes the importance of further understanding the distribution and potential risk of FiVs in the region.

microbiology↗

bioRxiv2023

Developmental Manganese Exposure Causes Lasting Attention Deficits Accompanied by Dysregulation of mTOR Signaling and Catecholaminergic Gene Expression in Brain Prefrontal Cortex

Elevated manganese (Mn) exposure is associated with attentional deficits in children, and is an environmental risk factor for attention deficit hyperactivity disorder (ADHD). We have shown that developmental Mn exposure causes lasting attention and sensorimotor deficits in a rat model of early childhood Mn exposure, and that these deficits are associated with a hypofunctioning catecholaminergic system in the prefrontal cortex (PFC), though the mechanistic basis for these deficits is not well understood. To address this, male Long-Evans rats were exposed orally to Mn (50 mg/kg/d) over PND 1-21 and attentional function was assessed in adulthood using the 5-Choice Serial Reaction Time Task. Targeted catecholaminergic system and epigenetic gene expression, followed by unbiased differential DNA methylation and gene regulation expression transcriptomics in the PFC, were performed in young adult littermates. Results show that developmental Mn exposure causes lasting focused attention deficits that are associated with reduced gene expression of tyrosine hydroxylase, dopamine transporter, and DNA methyltransferase 3a. Further, developmental Mn exposure causes broader lasting methylation and gene expression dysregulation associated with epigenetic regulation, inflammation, cell development, and hypofunctioning catecholaminergic neuronal systems. Pathway enrichment analyses uncovered mTOR and Wnt signaling pathway genes as significant transcriptomic regulators of the Mn altered transcriptome, and Western blot of total, C1 and C2 phospho-mTOR confirmed mTOR pathway dysregulation. Our findings deepen our understanding of the mechanistic basis of how developmental Mn exposure leads to lasting catecholaminergic dysfunction and attention deficits, which may aid future therapeutic interventions of environmental exposure associated disorders. Significance StatementAttention deficit hyperactivity disorder (ADHD) is associated with environmental risk factors, including exposure to neurotoxic agents. Here we used a rodent model of developmental manganese (Mn) exposure producing lasting attention deficits to show broad epigenetic and gene expression changes in the prefrontal cortex, and to identify disrupted mTOR and Wnt signaling pathways as a novel mechanism for how developmental Mn exposure may induce lasting attention and catecholaminergic system impairments. Importantly, our findings establish early development as a critical period of susceptibility to lasting deficits in attentional function caused by elevated environmental toxicant exposure. Given that environmental health threats disproportionately impact communities of color and low socioeconomic status, our findings can aid future studies to assess therapeutic interventions for vulnerable populations.

pharmacology and toxicology↗

bioRxiv2023

DNAGPT: A Generalized Pretrained Tool for Multiple DNA Sequence Analysis Tasks

Pre-trained large language models demonstrate potential in extracting information from DNA sequences, yet adapting to a variety of tasks and data modalities remains a challenge. To address this, we propose DNAGPT, a generalized DNA pre-training model trained on over 200 billion base pairs from all mammals. By enhancing the classic GPT model with a binary classification task (DNA sequence order), a numerical regression task (guanine-cytosine content prediction), and a comprehensive token language, DNAGPT can handle versatile DNA analysis tasks while processing both sequence and numerical data. Our evaluation of genomic signal and region recognition, mRNA abundance regression, and artificial genome generation tasks demonstrates DNAGPTs superior performance compared to existing models designed for specific downstream tasks, benefiting from pre-training using the newly designed model structure.

genomics↗

bioRxiv2023

Small RNAs from fungal pathogen Botrytis cinerea ride in extracellular vesicles to enter plant cells through clathrin-mediated endocytosis

Small RNAs (sRNAs) of the fungal pathogen Botrytis cinerea can enter plant cells and hijack host Argonaute protein 1 (AGO1) to silence host immunity genes. However, the mechanism by which these fungal sRNAs are secreted and enter host cells remains unclear. Here, we demonstrate that B. cinerea utilizes extracellular vesicles (EVs) to secrete Bc-sRNAs, which are then internalized by plant cells through clathrin-mediated endocytosis (CME). The B. cinerea tetraspanin protein, Punchless 1 (BcPLS1), serves as an EV biomarker and plays an essential role in fungal pathogenicity. We observe numerous Arabidopsis clathrin-coated vesicles (CCVs) around B. cinerea infection sites and the colocalization of B. cinerea EV marker BcPLS1 and Arabidopsis CLATHRIN LIGHT CHAIN 1, one of the core components of CCV. Meanwhile, BcPLS1 and the B. cinerea-secreted sRNAs are detected in purified CCVs after infection. Arabidopsis knockout mutants and inducible dominant-negative mutants of key components of CME pathway exhibit increased resistance to B. cinerea infection. Furthermore, Bc-sRNA loading into Arabidopsis AGO1 and host target gene suppression are attenuated in those CME mutants. Together, our results demonstrate that fungi secrete sRNAs via EVs, which then enter host plant cells mainly through CME.

plant biology↗

bioRxiv2023

Disease associated human TCR characterization by deep-learning framework TCR-DeepInsight

T cell function is defined by both T cell receptors (TCR) and T cell gene expression (GEX). Although single-cell technology enables the simultaneous capture of TCR and GEX information, the lack of a reference atlas and computational tools hinders our ability to uncover the fundamental TCR usage rules and to efficiently characterize disease-associated TCRs (dTCR). Here, through the collection of million-scale single-cell GEX-TCR reference atlas comprising 20 diverse disease conditions, we revealed the intrinsic features of TCR-MHC (Major Histocompatibility Complex) restriction in CD4/CD8 lineages. We observed the higher coherence for TCR/{beta} chains in memory T cells, and detected widely-existing public TCR/{beta} pairs across individuals. Building upon the reference atlas, we introduced TCR- DeepInsight, a deep-learning framework featuring a disease specificity scoring system that enables the characterization of dTCR clusters with similar GEX-TCR. Our study provides a valuable tool for researchers to analyze single-cell GEX-TCR data and identify dTCRs comprehensively and robustly.

bioinformatics↗

bioRxiv2023

Interspecies blastocyst complementation generates functional rat cell-derived forebrain tissues in mice

Interspecies organogenesis via blastocyst complementation provides a unique platform to study development in an evolutionarily context and holds potential to overcome world-wide organ shortages1. By using this technique, rat pancreas, thymus, heart, and eye tissues have been generated in mice2-4. To date, however, xeno-generation of brain tissues has not been achieved through blastocyst complementation. Here, we developed an optimized one-step blastocyst complementation strategy based on C-CRISPR5, which facilitated rapid screening of candidate genes to support blastocyst complementation. Among the seven WNT pathway-related genes selected for targeting, only Dkk1 or Hesx1 deficiency supported forebrain complementation by blastocyst injection of mouse embryonic stem cells (mESCs). Further, injecting rat ESCs (rESCs) into mouse blastocysts deficient for Hesx1 but not Dkk1 supported the development of adult chimeric forebrains comprised a large proportion of rat cells that were structurally and functionally similar to the mouse forebrains. Our analysis revealed that the rESC-derived forebrains developed along the spatial-temporal trajectory with the mouse forebrains rather than rat forebrains, but gene expression profiles of rESC-derived nerve cells surprisingly maintained the characteristics of the rat cells. We noted that the chimeric rate gradually decreased as development progressed, suggesting xenogeneic barriers during mid-to-late prenatal development. Interspecies forebrain complementation opens the door for studying evolutionarily conserved and divergent mechanisms underlying brain development and cognitive function. The C-CRIPSR based IBC strategy developed here holds great potential to broaden the study and application of interspecies organogenesis.

developmental biology↗

bioRxiv2023

TerC Proteins Function During Protein Secretion to Metalate Exoenzymes

Cytosolic metalloenzymes acquire metals from buffered intracellular pools. How exported metalloenzymes are appropriately metalated is less clear. We provide evidence that TerC family proteins function in metalation of enzymes during export through the general secretion (Sec-dependent) pathway. Bacillus subtilis strains lacking MeeF(YceF) and MeeY(YkoY) have a reduced capacity for protein export and a greatly reduced level of manganese (Mn) in the secreted proteome. MeeF and MeeY copurify with proteins of the general secretory pathway, and in their absence the FtsH membrane protease is essential for viability. MeeF and MeeY are also required for efficient function of the Mn2+-dependent lipoteichoic acid synthase (LtaS), a membrane-localized enzyme with an extracytoplasmic active site. Thus, MeeF and MeeY, representative of the widely conserved TerC family of membrane transporters, function in the co-translocational metalation of Mn2+-dependent membrane and extracellular enzymes.

microbiology↗

bioRxiv2023

Plasma cells in human pancreatic ductal adenocarcinoma secrete antibodies to self-antigens

Intratumoral B cell responses are associated with more favorable clinical outcomes in human pancreatic ductal adenocarcinoma (PDAC). However, the antigens driving these B cell responses are largely unknown. We sought to discover these antigens by using single-cell RNA sequencing (scRNA-Seq) and immunoglobulin (Ig) sequencing of tumor-infiltrating immune cells from seven primary PDAC samples. We identified activated T and B cell responses and evidence of germinal center reactions. Ig sequencing identified plasma cell (PC) clones expressing isotype-switched and hyper-mutated Igs, suggesting the occurrence of T cell-dependent B cell responses. We assessed the reactivity of 41 recombinant antibodies that represented the products of 235 PCs and 12 B cells toward multiple cell lines and PDAC tissues, and observed frequent staining of intracellular self-antigens. Three of these antigens were identified: the filamentous actin (F-actin), the nucleic protein, RUVBL2, and the mitochondrial protein, HSPD1. Antibody titers to F-actin and HSPD1 were elevated in the plasma of PDAC patients, and also detectable in healthy donors. Thus, PCs in PDAC produce auto-antibodies reacting with intracellular self-antigens, which may result from promotion of pre-existing, autoreactive B cell responses. These observations indicate that the chronic inflammatory microenvironment of PDAC can support the adaptive immune response.

cancer biology↗