Biology subjects

Engleman, E. G.

Publications and source records attributed to Engleman, E. G..

5 recordsLinked to original sources

bioRxiv2026

Successful dendritic cell vaccines require lasting in-situ TNF α secretion to license antitumor CD8 + T cell cytotoxicity

Dendritic cells (DCs) are central to activating cytotoxic CD8 T cells, yet DC-based vaccines have achieved limited success against established tumors. To address this gap, we analyzed the transcriptomic and functional changes CD8 T cells undergo following interactions with DC subsets in lymphoid organs and tumor sites. This approach allowed us to map their trajectory from naive to fully cytotoxic effector cells. We found that classical DCs in lymphoid organs provide essential antigen presentation but fail to elicit cytotoxicity. Instead, antigenexperienced CD8 T cells require additional inflammatory signals, primarily through TNF, delivered at tumor sites by infiltrating myeloid DCs. Effective cytotoxic responses therefore depend on the synchronization of these distinct, temporally separated signals. Notably, tumor antigen-pulsed DC vaccines rapidly lose TNF expression after infiltrating tumors, limiting their efficacy. These findings establish a sequential model of T cell activation and suggest strategies to enhance the potency of DC-based immunotherapies.

immunology↗

bioRxiv2026

A Pan-Cancer Single-Cell Atlas to Evaluate Tumor Identity, Cell Line Concordance, and Dependency Mapping

Bulk RNA sequencing enables pan-cancer transcriptional analyses, but obscures cancer cell-specific programs due to admixture with nonmalignant cells, thereby limiting direct comparison between experimental models and primary tumors. Single-cell RNA sequencing (scRNA-seq) overcomes these limitations; however, the biological interpretability of public datasets is often compromised by variable data quality, inconsistent annotation, and atlas-scale aggregation strategies that prioritize data volume over biological coherence. We therefore developed a stringent integration framework that prioritizes representative malignant transcriptional states. Using Mahalanobis distance-based selection within batch-corrected latent space, we constructed a pan-cancer atlas comprising 135,424 high-quality malignant cells from 499 samples across 36 adult and pediatric cancers. Atlas-derived cancer signatures were used to determine tumor-cell line concordance and project ElasticNet models trained on DepMap CRISPR screens to infer cancer-specific gene dependencies. The scTumor Atlas establishes a scalable framework for tumor identity inference, cancer cell line benchmarking, and systematic identification of genetic vulnerabilities.

cancer biology↗

bioRxiv2024

Rapid Sterilization of Clinical Apheresis Blood Products using Ultra-High Dose Rate Radiation

BACKGROUND AND OBJECTIVESApheresis platelets products and plasma are essential for medical interventions, but both still have inherent risks associated with contamination and viral transmission. Platelet products are vulnerable to bacterial contamination due to storage conditions, while plasma requires extensive screening to minimize virus transmission risks. Here we investigate rapid irradiation to sterilizing doses for bacteria and viruses as an innovative pathogen reduction technology. MATERIALS AND METHODSWe configured a clinical linear accelerator to deliver ultra-high dose rate (6 kGy/min) irradiation to platelet and plasma blood components. Platelet aliquots spiked with 105 CFU of E.coli were irradiated with 0.1-20 kGy, followed by E.coli growth and platelet count assays. COVID Convalescent Plasma (CCP) aliquots were irradiated at a virus-sterilizing dose of 25 kGy and subsequently, RBD- specific antibody binding was assessed. RESULTS1 kGy irradiation of bacteria-spiked platelets reduced E.coli growth by 2.7- log without significant change of platelet count, and 5 kGy or higher produced complete growth suppression. The estimated sterilization (6-log bacterial reduction) dose was 2.3 kGy, corresponding to 31% platelet count reduction. A 25 kGy virus sterilizing dose to CCP produced a 9.2% average drop of RBD-specific IgG binding. CONCLUSIONThis study shows proof-of-concept of a novel rapid blood sterilization technique using a clinical linear accelerator. Promising platelet counts and CCP antibody binding were maintained at bacteria and virus sterilizing doses, respectively. This represents a potential point-of-care blood product sterilization solution. If additional studies corroborate these findings, this may be a practical method for ensuring blood products safety. HIGHLIGHTSO_LI1 kGy irradiation of bacteria-spiked platelets reduced E.coli growth by 2.7-log without significant change of platelet count, and 5 kGy or higher produced complete growth suppression. C_LIO_LIThe estimated sterilization (6-log bacterial reduction) dose was 2.3 kGy, corresponding to 31% platelet count reduction. C_LIO_LIA 25 kGy virus sterilizing dose to CCP produced a 9.2% average drop of RBD- specific IgG binding. C_LI

microbiology↗

bioRxiv2022

Identification of cell types in multiplexed in situ images by combining protein expression and spatial information using CELESTA reveals novel spatial biology

Advances in multiplexed in situ imaging are revealing important insights in spatial biology. However, cell type identification remains a major challenge in imaging analysis, with most existing methods involving substantial manual assessment and subjective decisions for thousands of cells. We propose a novel machine learning algorithm, CELESTA, which uses both cells protein expression and spatial information to identify cell type of individual cells. We demonstrate the performance of CELESTA on multiplexed immunofluorescence in situ images of colorectal cancer and head and neck cancer. Using the cell types identified by CELESTA, we identify tissue architecture associated with lymph node metastasis in HNSCC, which we validate in an independent cohort. By coupling our in situ spatial analysis with single-cell RNA-sequencing data on proximal sections of the same tissue specimens, we identify and validate cell-cell crosstalk associated with lymph node metastasis, demonstrating the power of spatial biology to reveal clinically-relevant cellular interactions.

bioinformatics↗

bioRxiv2020

Hyaluronan Synthesis Inhibition Impairs Antigen Presentation and Delays Transplantation Rejection

A coat of pericellular hyaluronan surrounds mature dendritic cells (DC) and contributes to cell-cell interactions. We asked whether 4-methylumbelliferone (4MU), an oral inhibitor of HA synthesis, could inhibit antigen presentation. We find that 4MU treatment reduces pericellular hyaluronan, destabilizes interactions between DC and T-cells, and prevents T-cell proliferation in vitro and in vivo. These effects were observed only when 4MU was added prior to initial antigen presentation but not later, consistent with 4MU-mediated inhibition of de novo antigenic responses. Building on these findings, we find that 4MU delays rejection of allogeneic pancreatic islet transplant and allogeneic cardiac transplants in mice and suppresses allogeneic T-cell activation in human mixed lymphocyte reactions. We conclude that 4MU, an approved drug, may have benefit as an adjunctive agent to delay transplantation rejection.

immunology↗