OH2 oncolytic virus: A novel approach to glioblastoma intervention through direct targeting of tumor cells and augmentation of anti-tumor immune responses.

Glioblastoma (GBM), the deadliest central nervous system cancer, presents a poor prognosis and scant therapeutic options. Our research spotlights OH2, an oncolytic viral therapy derived from herpes simplex virus 2 (HSV-2), which demonstrates substantial antitumor activity and favorable tolerance in GBM. The extraordinary efficacy of OH2 emanates from its unique mechanisms: it selectively targets tumor cells replication, powerfully induces cytotoxic DNA damage stress, and kindles anti-tumor immune responses. Through single-cell RNA sequencing analysis, we discovered that OH2 not only curtails the proliferation of cancer cells and tumor-associated macrophages (TAM)-M2 but also bolsters the infiltration of macrophages, CD4+ and CD8+ T cells. Further investigation into molecular characteristics affecting OH2 sensitivity revealed potential influencers such as TTN, HMCN2 or IRS4 mutations, CDKN2A/B deletion and IDO1 amplification. This study marks the first demonstration of an HSV-2 derived OV's effectiveness against GBM. Significantly, these discoveries have driven the initiation of a phase I/II clinical trial (ClinicalTrials.gov: NCT05235074). This trial is designed to explore the potential of OH2 as a therapeutic option for patients with recurrent central nervous system tumors following surgical intervention.

PHF6 maintains acute myeloid leukemia via regulating NF-κB signaling pathway.

Acute myeloid leukemia (AML) is a major hematopoietic malignancy characterized by the accumulation of immature and abnormally differentiated myeloid cells in bone marrow. Here with in vivo and in vitro models, we demonstrate that the Plant homeodomain finger gene 6 (PHF6) plays an important role in apoptosis and proliferation in myeloid leukemia. Phf6 deficiency could delay the progression of RUNX1-ETO9a and MLL-AF9-induced AML in mice. PHF6 depletion inhibited the NF-κB signaling pathways by disrupting the PHF6-p50 complex and partially inhibiting the nuclear translocation of p50 to suppress the expression of BCL2. Treating PHF6 over-expressed myeloid leukemia cells with NF-κB inhibitor (BAY11-7082) significantly increased their apoptosis and decreased their proliferation. Taken together, in contrast to PHF6 as a tumor suppressor in T-ALL as reported, we found that PHF6 also plays a pro-oncogenic role in myeloid leukemia, and thus potentially to be a therapeutic target for treating myeloid leukemia patients.

lncRNA TRHDE-AS1 Correlated with Genomic Landscape and Clinical Outcome in Glioma.

The role of lncRNA in cancer development has received more and more attention in research. A variety of lncRNAs are associated with the occurrence and development of glioma. However, the role of TRHDE-AS1 in glioma is still unknown. In this study, we explored the role of TRHDE-AS1 in glioma through bioinformatic methods. We first identified an association between TRHDE-AS1 and tumor prognosis in pan-cancer analysis. Subsequently, the expression levels of TRHDE-AS1 in various clinical types of glioma were compared, and significant differences were found in pathological classification, WHO classification, molecular classification, IDH mutation, and age stratification. We analyzed the genes co-expressed with TRHDE-AS1 in glioma. In the functional analysis of TRHDE-AS1, we found that TRHDE-AS1 may be involved in the regulation of synapse-related functions. In glioma cancer driver gene correlation analysis, it was also found that TRHDE-AS1 was significantly correlated with the expression levels of multiple driver genes such as TP53, BRAF, and IDH1. By comparing the mutant profiles of the high and low TRHDE-AS1 groups, we also found that there may be differences in TP53 and CIC gene mutations in low-grade gliomas. Subsequent correlation analysis between TRHDE-AS1 and glioma immune microenvironment showed that the expression level of TRHDE-AS1 was correlated with a variety of immune cells. Therefore, we believe that TRHDE-AS1 is involved in the occurrence and development of glioma and has the ability to predict the prognosis of glioma as a biomarker of glioma.

PHF6 promotes the progression of endometrial carcinoma by increasing cancer cells growth and decreasing T-cell infiltration.

Uterine corpus endometrial carcinoma (UCEC) is the most common cancer of the female reproductive tract. The overall survival of advanced and recurrent UCEC patients is still unfavourable nowadays. It is urgent to find a predictive biomarker and block tumorgenesis at an early stage. Plant homeodomain finger protein 6 (PHF6) is a key player in epigenetic regulation, and its alterations lead to various diseases, including tumours. Here, we found that PHF6 expression was upregulated in UCEC tissues compared with normal tissues. The UCEC patients with high PHF6 expression had poor survival than UCEC patients with low PHF6 expression. PHF6 mutation occurred in 12% of UCEC patients, and PHF6 mutation predicted favourable clinical outcome in UCEC patients. Depletion of PHF6 effectively inhibited HEC-1-A and KLE cell proliferation in vitro and decreased HEC-1-A cell growth in vivo. Furthermore, high PHF6 level indicated a subtype of UCECs characterized by low immune infiltration, such as CD3+ T-cell infiltration. While knockdown of PHF6 in endometrial carcinoma cells increased T-cell migration by promoting IL32 production and secretion. Taken together, our findings suggested that PHF6 might play an oncogenic role in UCEC patients. Thus, PHF6 could be a potential biomarker in predicting the prognosis of UCEC patients. Depletion of PHF6 may be a novel therapeutic strategy for UCEC patients.

Elevated TAF12 Expression Predicts Poor Prognosis in Glioma Patients: Evidence from Bioinformatic and Immunohistochemical Analyses.

TATA box-binding protein-associated factor 12 (TAF12) has been identified as an oncogene in choroid plexus carcinoma, but its role in glioma is poorly understood because of a lack of previous studies. This study investigated the relationship of TAF12 expression with the clinicopathologic features of glioma cases, as well as its prognostic value and biological function, using large-scale databases and clinical samples. TAF12 mRNA expression and clinicopathologic characteristics of glioma cases were assessed in three public databases, and bioinformatics analyses were conducted to explore the prognostic value and biological functions of TAF12 in glioma. High TAF12 expression was commonly associated with reduced survival time and poor clinical indexes, including higher World Health Organization grade, wild-type isocitrate dehydrogenase 1 expression, and 1p19q non-codeletion status (p < 0.0001). Multivariate Cox regression analysis showed that high TAF12 expression was an independent poor prognostic factor for glioma patients (hazard ratio = 1.41, 95% confidence interval, 1.18-1.68, p < 0.001). Functional enrichment analysis revealed involvement of TAF12 in immune and inflammatory responses in glioma. Also, expression of several immune checkpoint molecules was significantly higher in samples with high TAF12 expression. TAF12 is a potential independent prognostic factor for glioma, and these findings provide a foundation for further investigation of the potential role of TAF12 in immunotherapy.