Biology subjects

Cheong, S. C.

Publications and source records attributed to Cheong, S. C..

3 recordsLinked to original sources

bioRxiv2026

Epstein-Barr virus co-opts ADAR1 to evade PKR activation of the integrated stress response in nasopharyngeal carcinoma

Viruses generate immunogenic double-stranded RNA (dsRNA) during their life cycle, necessitating mechanisms to evade host innate immune detection. Protein kinase R (PKR) is a pattern recognition receptor (PRR) that senses viral dsRNA and activates the host integrated stress response (ISR) by phosphorylating eukaryotic initiation factor 2 (eIF2) on its alpha subunit, causing global mRNA translation arrest. Viruses evade activation of the ISR and translation shut-down to facilitate replication. Adenosine deaminase acting on RNA 1 (ADAR1) is uniquely positioned to support viral replication due to its ability to convert adenosine (A) into inosine (I) inside dsRNA, thereby disrupting base-pair matching and preventing PKR activation. Here, we discovered that Epstein-Barr virus (EBV), the oncogenic driver of nasopharyngeal carcinoma (NPC), requires ADAR1 both to maintain latent infection and for lytic reactivation by preventing PKR-mediated ISR activation. EBV lytic reactivation stimulated viral protein expression, which was attenuated in the absence of ADAR1. Importantly, lytic reactivation or treatment of synthetic dsRNA in the absence of ADAR1 induced phosphorylation of eIF2 by PKR, stress granule formation, and caused cancer cell lethality without the production of virion progeny. Together these findings support a strategy for EBV lytic induction therapy in NPC without viral dissemination by exposing EBV to endogenous PRRs through ADAR1 inhibition.

cancer biology↗

bioRxiv2026

Dual-antigen Doggybone DNA vaccine induces potent anti-tumor immunity against immunosuppressive oral cancer

Anti-PD1 blockade benefits only a subset of patients with head and neck squamous cell carcinoma (HNSCC), highlighting the need for approaches that overcome tumor immune resistance. Here, using the doggybone DNA (dbDNATM) platform, we developed CaVac OPT, an optimized dual-antigen DNA vaccine targeting MAGED4B and FJX1, which are overexpressed in most HPV-negative HNSCC and multiple solid tumors. In the MOC-2 oral cancer model, CaVac OPT significantly reduced tumor growth and when combined with anti-PD1 therapy, further delayed progression and improved survival. Immune profiling showed increased infiltration of CD4+ and CD8+ T cells, expansion of stem-like Tcf1+ populations, without increase in regulatory T cells, a reduced M2/M1 macrophage ratio and activation of interferon gamma associated pathways with suppression of tumor-promoting signals. These findings demonstrate that CaVac OPT reprograms the tumor microenvironment, converting cold HNSCC into T cell-inflamed responsive tumors. CaVac OPT represents a promising strategy for achieving durable control of aggressive, immunotherapy-resistant head and neck cancer.

cancer biology↗

bioRxiv2025

Structural patterns and transcriptional effects of integrated Epstein-Barr virus revealed by long-read sequencing and RNA-sequencing in Nasopharyngeal Carcinoma

Integration of Epstein-Barr virus (EBV) DNA into the human genome is a critical event in nasopharyngeal carcinogenesis. Here, we comprehensively characterize large-scale virus-human integration events in four EBV-positive nasopharyngeal carcinoma (NPC) cell lines and tumors using Nanopore long-read sequencing technology. We identified four distinct integration types, with Type I being particularly notable, characterized by continuous long reads covering nearly the entire EBV genome. Our findings reveal the involvement of multiple integration events in inducing inter-chromosomal translocations, leading to significant genomic disruption through chromosomal rearrangements. Additionally, we explore the relationship between EBV integration sites and structural variations, further supporting the role of EBV integration in driving genomic instability. By integrating RNA-seq data, we demonstrate the potential for EBV integration to disrupt gene expression, highlighting several integration sites within cancer-associated genes such as CD96, ARHGAP27, ASH1L, KDM3B, ZMYM2, and PIK3C2A. Notably, EBV-human fusion events were prevalent in EBV-associated NPCs, including intriguing fusion transcripts such as LRRC8C-RPMS1 and LINC00486-RPMS1, which provide further evidence of the oncogenic potential of EBV integration. Taken together, this study uncovers EBV integration patterns in Nasopharyngeal carcinogenesis using long-read sequencing technology.

cancer biology↗