Peripheral B cells from patients with hepatitis C virus-associated lymphoma exhibit clonal expansion and an anergic-like transcriptional profile.

Chronic HCV infection remains a global health concern due to its involvement in hepatic and extrahepatic diseases, including B cell non-Hodgkin lymphoma (BNHL). Clinical and epidemiological evidence support a causal role for HCV in BNHL development, although mechanistic insight is lacking. We performed RNA-sequencing on peripheral B cells from patients with HCV alone, BNHL alone, and HCV-associated BNHL to identify unique and shared transcriptional profiles associated with transformation.

Cancer genes disfavoring T cell immunity identified via integrated systems approach.

Adoptive T cell therapies (ACT) have been curative for a limited number of cancer patients. The sensitization of cancer cells to T cell killing may expand the benefit of these therapies for more patients. To this end, we use a three-step approach to identify cancer genes that disfavor T cell immunity.

Immunomagnetic B cell isolation as a tool to study blood cell subsets and enrich B cell transcripts.

Objective: Transcriptional profiling of immune cells is an indispensable tool in biomedical research; however, heterogenous sample types routinely used in transcriptomic studies may mask important cell type-specific transcriptional differences. Techniques to isolate desired cell types are used to overcome this limitation. We sought to evaluate the use of immunomagnetic B cell isolation on RNA quality and transcriptional output.

Naturally Acquired SARS-CoV-2 Immunity Persists for Up to 11 Months Following Infection.

Background: Characterizing the kinetics of the antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of critical importance to developing strategies that may mitigate the public health burden of coronavirus disease 2019 (COVID-19). We conducted a prospective, longitudinal analysis of COVID-19 convalescent plasma donors at multiple time points over an 11-month period to determine how circulating antibody levels change over time following natural infection.

Methods: From April 2020 to February 2021, we enrolled 228 donors.

Anti-SARS-CoV-2 Serology persistence over time in COVID-19 Convalescent Plasma Donors.

Background: Characterizing the kinetics of the antibody response to SARS□CoV□2 is of critical importance to developing strategies that may mitigate the public health burden of COVID-19. We sought to determine how circulating antibody levels change over time following natural infection.

Methods/materials: We conducted a prospective, longitudinal analysis of COVID-19 convalescent plasma (CCP) donors at multiple time points over a 9-month period.

Multi-phenotype CRISPR-Cas9 Screen Identifies p38 Kinase as a Target for Adoptive Immunotherapies.

T cells are central to all currently effective cancer immunotherapies, but the characteristics defining therapeutically effective anti-tumor T cells have not been comprehensively elucidated. Here, we delineate four phenotypic qualities of effective anti-tumor T cells: cell expansion, differentiation, oxidative stress, and genomic stress. Using a CRISPR-Cas9-based genetic screen of primary T cells we measured the multi-phenotypic impact of disrupting 25 T cell receptor-driven kinases.

Host conditioning with IL-1β improves the antitumor function of adoptively transferred T cells.

Host conditioning has emerged as an important component of effective adoptive cell transfer-based immunotherapy for cancer. High levels of IL-1β are induced by host conditioning, but its impact on the antitumor function of T cells remains unclear. We found that the administration of IL-1β increased the population size and functionality of adoptively transferred T cells within the tumor.

Augmenting subnetwork inference with information extracted from the scientific literature.

Many biological studies involve either (i) manipulating some aspect of a cell or its environment and then simultaneously measuring the effect on thousands of genes, or (ii) systematically manipulating each gene and then measuring the effect on some response of interest. A common challenge that arises in these studies is to explain how genes identified as relevant in the given experiment are organized into a subnetwork that accounts for the response of interest. The task of inferring a subnetwork is typically dependent on the information available in publicly available, structured databases, which suffer from incompleteness.

Generation of Tumor Antigen-Specific iPSC-Derived Thymic Emigrants Using a 3D Thymic Culture System.

Induced pluripotent stem cell (iPSC)-derived T cells may provide future therapies for cancer patients, but those generated by current methods, such as the OP9/DLL1 system, have shown abnormalities that pose major barriers for clinical translation. Our data indicate that these iPSC-derived CD8 single-positive T cells are more like CD4CD8 double-positive T cells than mature naive T cells because they display phenotypic markers of developmental arrest and an innate-like phenotype after stimulation. We developed a 3D thymic culture system to avoid these aberrant developmental fates, generating a homogeneous subset of CD8αβ antigen-specific T cells, designated iPSC-derived thymic emigrants (iTEs).

Epigenetic control of CD8 T cell differentiation.

Upon stimulation, small numbers of naive CD8 T cells proliferate and differentiate into a variety of memory and effector cell types. CD8 T cells can persist for years and kill tumour cells and virally infected cells. The functional and phenotypic changes that occur during CD8 T cell differentiation are well characterized, but the epigenetic states that underlie these changes are incompletely understood.

The Non-coding Mammary Carcinoma Susceptibility Locus, Mcs5c, Regulates Pappa Expression via Age-Specific Chromatin Folding and Allele-Dependent DNA Methylation.

In understanding the etiology of breast cancer, the contributions of both genetic and environmental risk factors are further complicated by the impact of breast developmental stage. Specifically, the time period ranging from childhood to young adulthood represents a critical developmental window in a woman's life when she is more susceptible to environmental hazards that may affect future breast cancer risk. Although the effects of environmental exposures during particular developmental Windows of Susceptibility (WOS) are well documented, the genetic mechanisms governing these interactions are largely unknown.

5-hydroxymethylation of the EBV genome regulates the latent to lytic switch.

Latent Epstein-Barr virus (EBV) infection and cellular hypermethylation are hallmarks of undifferentiated nasopharyngeal carcinoma (NPC). However, EBV infection of normal oral epithelial cells is confined to differentiated cells and is lytic. Here we demonstrate that the EBV genome can become 5-hydroxymethylated and that this DNA modification affects EBV lytic reactivation.