Breaking the oncogene-immune suppression cycle through dual HER2 silencing and innate immune activation by biomineralized DNA nanocomplexes.

Tumor microenvironment activatable immunomodulator for cancer immunotherapy.

Ginsenoside Rh1 sensitizes gastric cancer to cuproptosis and represses immune evasion.

Advances in current and emerging immunotherapies for ovarian cancer.

LONP1, a mitochondrial ATP-dependent protease, plays a crucial role in mitochondrial homeostasis by regulating protein turnover and mitophagy. Recent studies have highlighted its upregulation in various cancers, including colorectal cancer (CRC). This study investigates the expression of LONP1 in colon adenocarcinoma (COAD) and its correlation with mitophagy-related proteins and immune infiltration markers. Using publicly available databases and immunohistochemical analysis of 50 COAD patient samples, we confirmed that LONP1 expression is significantly elevated in COAD compared with normal tissue. High LONP1 levels were associated with tumor progression, TP53 mutation status, and poor prognosis. Correlation analyses revealed that LONP1 is closely linked to mitochondrial dynamics, mitophagy regulators (PINK1, AMBRA1, FUNDC1), and metabolic reprogramming. Additionally, LONP1 expression positively correlated with tumor-infiltrating lymphocytes, particularly CD8+ T cells, suggesting a potential role in immune evasion. Immunohistochemical analysis distinguished two patterns: high LONP1/low TOMM20 expression associated with aggressive tumors and low LONP1/high TOMM20 expression linked to better outcomes and stronger immune infiltration. These findings suggest that LONP1 contributes to tumor progression through mitochondrial regulation and immune modulation, highlighting its potential as both a prognostic biomarker and a therapeutic target in COAD.

Mitochondrial metabolic vulnerabilities in high-grade serous ovarian cancer.

Dual-targeted NIR-II AIE theranostic nanoparticles disrupt HNRNPC-driven ITGA1+ myCAFs differentiation and immune evasion in oral squamous cell carcinoma.

Perineural invasion in head and neck squamous cell carcinoma: Neuro-immune mechanisms driving immunotherapy resistance and emerging therapeutic strategies.

Immune checkpoint blockade, exemplified by anti-PD-L1 antibody (αPD-L1), has revolutionized cancer immunotherapy. Nevertheless, its therapeutic potential is constrained by the inherently low tumor immunogenicity and the persistence of cancer stem cells (CSCs), which drive immune escape and tumor recurrence. Here, a CSC-targeted, pH-sensitive liposomal nano-cocktail of doxorubicin and bufalin (PSLB/D), was demonstrated to elicit robust immunogenic cell death (ICD), thereby potentiating the efficacy of αPD-L1 in immunologically 'cold' triple-negative breast cancer (TNBC) models. The PSLB/D itself demonstrated potent synergistic tumor-inhibitory effects in both cell lines and 3-D tumor spheroids, and effectively eliminated CSCs, with 85-90% reductions in both primary and secondary sphere formation. Deep penetration and robust ICD-mediated immune response were observed in patient-derived organoids, highlighting its translational potential. The therapeutic efficacy was validated in immunocompromised MDA-MB-231 and immunocompetent 4T1 orthotopic mouse models. Notably, in immunocompetent 4T1 models, PSLB/D induced strong expression of calreticulin, leading to the recruitment of dendritic cells and cytotoxic CD8⁺ T cells. Activation of these immune cells converted the immunosuppressive 'cold' tumors into immunogenic 'hot' ones, substantially amplifying the effectiveness of αPD-L1. This chemo-immunotherapy also generated memory T cells, suggesting the potential for longer antitumor immune responses. STATEMENT OF SIGNIFICANCE: Cancer recurrence and immune evasion in triple-negative breast cancer (TNBC) are largely driven by resilient cancer stem cells (CSCs). This study introduces a pH-sensitive liposomal nano-cocktail composed of doxorubicin and a CSC inhibitor, specifically engineered to overcome the immunosuppressive tumor microenvironment. We demonstrate that this nanococktail triggers potent immunogenic cell death (ICD) in patient-derived organoids and orthotopic models, exceeding the efficacy of conventional formulations or monotherapy. By successfully converting "cold" TNBC tumors into immunologically "hot", the nano-cocktail significantly amplifies anti-PD-L1 immunotherapy outcomes. These findings offer a compelling evidence-based framework for integrating targeted nanomedicine with clinical chemo-immunotherapy protocols to prevent recurrence.

Oncogenic viruses cause approximately 20% of cancers globally burden, with Epstein-Barr virus and high-risk Human papillomavirus recognized as major contributors to epithelial malignancies. Increasing evidence suggests that EBV-HPV co-infection may enhance tumour progression through overlapping molecular and immunological mechanisms, particularly in cervical, oropharyngeal, and nasopharyngeal cancers. This review critically summarizes current evidence regarding the cooperative role of EBV and HPV in carcinogenesis while distinguishing viral co-presence from biologically active co-infection. EBV latent proteins, including LMP1, LMP2A, and EBNA1, activate oncogenic signalling pathways such as NF-κB, PI3K/Akt, and JAK/STAT, whereas HPV oncoproteins E6 and E7 disrupt p53 and retinoblastoma (Rb) tumour suppressor pathways. Together, these alterations may promote genomic instability, chronic inflammation, immune evasion, epigenetic dysregulation, and epithelial-mesenchymal transition (EMT), thereby enhancing invasive and metastatic potential. Epidemiological studies report higher frequencies of EBV-HPV co-detection in advanced lesions and aggressive tumours; however, causal synergy remains insufficiently validated because of methodological heterogeneity and variability in viral detection techniques, including PCR, in situ hybridization, and immunohistochemistry. Emerging technologies such as spatial transcriptomics and single-cell profiling may improve characterization of biologically meaningful co-infection. In addition, circulating viral DNA, viral microRNAs, and HPV genotyping are being explored as biomarkers for disease monitoring and prognosis. Therapeutic strategies targeting viral oncogenes, immune checkpoints, and gene-editing technologies also represent promising investigational approaches. Overall, EBV-HPV co-infection represents a biologically plausible but incompletely understood contributor to tumour aggressiveness, emphasizing the need for standardized diagnostics, longitudinal studies, and functional experimentalmodels.

Alphaviruses, including significant human pathogens like Chikungunya (CHIKV), Venezuelan Equine Encephalitis (VEEV), and the model Sindbis virus (SINV), pose a considerable global health threat. Their ability to establish infection and cause disease is critically dependent on successfully subverting the host's innate immune defenses, particularly the Type I Interferon (IFN-I) system. This review provides a comparative analysis of the molecular strategies employed by CHIKV, VEEV, and SINV to dismantle these antiviral pathways. We first outline the conserved principles that form a core alphavirus "toolkit" for evasion, such as the formation of membrane-bound replication factories to shield viral RNA from cytosolic sensors and NSP1-mediated mRNA capping to mimic host transcripts. The review then delves into the divergent, virus-specific tactics, highlighting the central role of the non-structural protein 2 (NSP2) as a master antagonist. We contrast the aggressive strategies of pathogenic alphaviruses-such as CHIKV NSP2-mediated cleavage of MAVS and degradation of STAT2, and VEEV-induced degradation of STAT1-with the more subtle, modulatory approach of SINV, which relies more on a global shutdown of host gene expression. These distinct molecular mechanisms are directly correlated with their varying pathogenic outcomes. Furthermore, we examine the remarkable adaptability of these strategies between vertebrate hosts, where suppressing the IFN system is paramount, and invertebrate vectors, where evading the RNAi pathway is the primary challenge. A comprehensive understanding of these commonalities and divergences in immune evasion is essential for the rational design of broad-spectrum antiviral therapeutics and next-generation vaccines.

All screens lead to polo-like kinase 1: A central node in cancer therapeutics and resistance.

Chronic viral hepatitis caused by hepatitis B virus (HBV) and hepatitis C virus (HCV) remains a leading global public health burden, driving progressive liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC) through complex interactions between viral replication, host immune responses, and extracellular matrix (ECM) remodelling. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that serve as central regulators of ECM homoeostasis and immune modulation in the liver. While physiological MMP activity is essential for tissue repair and immune surveillance, dysregulation of the MMP/TIMP (tissue inhibitors of metalloproteinases) axis during viral hepatitis promotes hepatic fibrogenesis, immune evasion, and malignant transformation, positioning MMPs as both drivers of disease progression and promising therapeutic targets. This review comprehensively examines the molecular and cellular mechanisms governing MMP/TIMP dysregulation across the spectrum of viral hepatitis, with particular focus on HCV and HBV. We address the reciprocal interactions between these viruses and MMP/TIMP expression, the roles of MMPs in liver fibrosis, viral replication, hepatocarcinogenesis, and immunomodulation of the tumour microenvironment, and the accelerated fibrogenic mechanisms in HIV-HCV and HIV-HBV coinfection. The review also extends to acute viral hepatitis (HAV and HEV), where direct MMP/TIMP data remain scarce but mechanistic and indirect ECM evidence indicate significant involvement. Finally, we critically evaluate current and emerging MMP-targeted therapeutic strategies including selective inhibitors, nanoparticle delivery systems, and RNA-based approaches and highlight key unresolved questions to guide future research towards disease-tailored interventions against viral hepatitis-driven liver damage and malignant progression.

A nanosystem targeting genomic instability and mitochondrial damage to stimulate STING pathway for synergistic immunotherapy for advanced prostate cancer.

Triple-negative breast cancer (TNBC) is an aggressive subtype lacking estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression, with limited treatment options. Tumor-associated macrophages (TAMs), as key immune cells in the tumor microenvironment, exacerbate the malignancy of TNBC by promoting angiogenesis, metastasis, immune evasion, and drug resistance. We systematically searched PubMed, Web of Science, and ClinicalTrials.gov databases to collect clinical trials targeting TAMs for the treatment of TNBC. Data from completed and ongoing studies were extracted and analyzed, focusing on strategies that inhibit macrophage recruitment, clearance, and reprogramming, as well as their combination with standard therapies. TAMs in TNBC predominantly exhibit an M2-like pro-tumor phenotype, originating from circulating monocytes and tissue-resident macrophages, and drive progression through multiple pathways. Clinical trials indicate preliminary efficacy for strategies including CSF-1/CSF-1R inhibitors, bisphosphonates, and reprogramming agents-particularly when combined with chemotherapy or immune checkpoint inhibitors-though response rates vary, and optimal regimens remain under investigation. TAMs represent a promising therapeutic target in TNBC. Emerging clinical evidence supports the potential of targeted therapies against them, though further optimization of patient selection and combination strategies is required. This review provides a systematic foundation for advancing treatments targeting TAMs. We confirm that the scientific content remains unchanged.

Prostate cancer (PCa) is one of the most common malignancies in men and remains particularly challenging as it progresses to the castration-resistant stage. Increasing evidence indicates that dysregulated RNA editing plays an active role in PCa progression and resistance to therapy. Among these modifications, adenosine-to-inosine editing catalyzed by adenosine deaminase acting on RNA 1 (ADAR1) alters transcripts, such as androgen receptor (AR) and antizyme inhibitor 1, promoting androgen-independent growth, metastasis, and immune evasion. Conversely, cytidine-to-uridine editing mediated by apolipoprotein B mRNA editing catalytic polypeptide-like 3 (APOBEC3) enzymes contributes to genomic instability. For example, APOBEC3B induces mutagenesis and resistance to AR-targeted therapy, and APOBEC3C functions as a context-dependent tumor suppressor that is transcriptionally repressed by the AR in advanced disease. Clinically, RNA editing signatures, including APOBEC3C expression levels, have shown promise as biomarkers for risk stratification, disease monitoring, and prognosis. Therapeutically, inhibition of ADAR1 or APOBEC3B, restoration of APOBEC3C activity, and site-specific corrective RNA editing using the CRISPR-ADAR2 platform represent emerging precision strategies. Ongoing development of small-molecule inhibitors, oligonucleotide-based modulators, and liquid biopsy-based detection methods further highlights the translational relevance of RNA editing in PCa. Future research should focus on improving editing specificity, minimizing off-target effects, and validating these biomarkers and therapeutic targets in clinical settings to fully realize the diagnostic and therapeutic potential of RNA editing in the precise management of prostate cancer.

Mitochondrial RNA helicase DDX28 promotes cell cycle and DNA repair programs and shapes an immunosuppressive microenvironment in acute myeloid leukemia.

West Nile Virus inhibits type I interferon response via TRIM71 in human microglial cells.

Cysteine proteases in oral potentially malignant disorders: Molecular drivers, diagnostic signatures, and therapeutic opportunities.

Tumor immune microenvironment in cervical cancer: Histological subtype-specific immune landscapes and therapeutic implications.