Biology subjects

Luu, T. T.

Publications and source records attributed to Luu, T. T..

3 recordsLinked to original sources

bioRxiv2025

Integrated single cell analysis identifies CD39+ tumor-associated NK cells with cytotoxic potential in lung cancer

Natural killer (NK) cell-targeting immunotherapies are emerging, yet the differentiation and functional states of tumor-infiltrating NK cells remain poorly understood. Using matched single-nucleus RNA and ATAC sequencing of non-small cell lung cancer (NSCLC) specimens, we resolved the transcriptional and epigenetic landscape of intratumoral NK cells. We identified two tumor-associated NK (taNK) cell subsets marked by ITGAE (CD103) and ITGA1 (CD49a) that display features of tissue residency and dysfunction while preserving cytotoxic function. Trajectory and regulon analyses revealed an inflammation-driven transition from early GZMK NKs toward an ENTPD1+ (CD39) effector state characterized by interferon-stimulated gene (ISG) programs. Functional profiling established CD39 taNK as the dominant cytotoxic NK cell population with superior killing capacity that is further potentiated by NKG2A blockade. This study offers mechanistic insights into NK cell differentiation in NSCLC and establishes CD39 taNK cells as a targetable effector population for immunotherapy. One sentence summaryMultiomic analysis identifies CD39+ tumor-associated NK cells as a cytotoxic effector state in NSCLC responsive to NKG2A blockade.

immunology↗

bioRxiv2022

Control of NK cell tolerance in MHC class I-deficiency by regulated SHP-1 localization to the activating immune synapse

Signaling via inhibitory KIR/Ly49 receptors preserves natural killer (NK) cell self-tolerance but also conveys NK cell reactivity towards MHC class-I low target cells in an education process. Here, we demonstrate that mouse NK cell education by H-2Dd regulates transcription of several genes in Ly49A+ NK cells including Ptpn6, encoding the phosphatase SHP-1. SHP-1 was highly expressed in uneducated NK cells, in which knock-out of Ptpn6 increased responsiveness. Following NKp46 triggering of uneducated NK cells, a higher synaptic abundance of phosphorylated SHP-1 was found relative to educated NK cells, concomitant with reduced phosphorylation of several signaling molecules, including PLC-g2, SLP-76, ZAP70/Syk and ERK1/2. SHP-1 overlapped extensively with F-actin and SLP-76 in the uneducated activating synapse of Ly49A+ NK cells, whereas a greater association between Ly49A and SHP-1 was observed in educated NK cells. Thus, our results indicate that in addition to transcriptional regulation, a distinct SHP-1 patterning in NK cell activating synapses can determine their tolerance.

immunology↗

bioRxiv2020

WHOLE-GENOME SEQUENCING AND DE NOVO ASSEMBLY OF A 2019 NOVEL CORONAVIRUS (SARS-COV-2) STRAIN ISOLATED IN VIETNAM

The pandemic COVID-19 caused by the zoonotic virus SARS-CoV-2 has devastated countries worldwide, infecting more than 4.5 million people and leading to more than 300,000 deaths. Whole genome sequencing (WGS) is an effective tool to monitor emerging strains and provide information for intervention, thus help to inform outbreak control decisions. Here, we reported the first effort to sequence and de novo assemble the whole genome of SARS-CoV-2 using PacBios SMRT sequencing technology in Vietnam. We also presented the annotation results and a brief analysis of the variants found in our SARS-CoV-2 strain, which was isolated from a Vietnamese patient. The sequencing was successfully completed and de novo assembled in less than 30 hours, resulting in one contig with no gap and a length of 29,766 bp. All detected variants as compared to the NCBI reference were highly accurate as confirmed by Sanger sequencing. The results have shown the potential of long read sequencing to provide high quality WGS data to support public health responses, and advance understanding of this and future pandemics.

genomics↗