Search Results (1,017)

Cancer disparities in low- and middle-income countries (LMICs) arise from multifaceted interactions between environmental exposures, infectious agents, and systemic inequities, such as limited access to care. The exposome, a framework encompassing the totality of non-genetic exposures throughout life, offers a powerful lens for understanding these disparities. In LMICs, populations are disproportionately affected by air and water pollution, occupational hazards, and oncogenic infections, including human papillomavirus (HPV), hepatitis B virus (HBV), Helicobacter pylori (H. pylori), human immunodeficiency virus (HIV), and neglected tropical diseases, such as schistosomiasis. These infectious agents contribute to increased cancer susceptibility and poor outcomes, particularly in immunocompromised individuals. Moreover, climate change, food insecurity, and barriers to healthcare access exacerbate these risks. This review adopts a population-level exposome approach to explore how environmental and infectious exposures intersect with genetic, epigenetic, and immune mechanisms to influence cancer incidence and progression in LMICs. We highlight the critical pathways linking chronic exposure and inflammation to tumor development and evaluate strategies such as HPV and HBV vaccination, antiretroviral therapy, and environmental regulation. Special attention is given to tools such as exposome-wide association studies (ExWASs), which offer promise for exposure surveillance, early detection, and public health policy. By integrating exposomic insights into national health systems, especially in regions such as sub-Saharan Africa (SSA) and South Asia, LMICs can advance equitable cancer prevention and control strategies. A holistic, exposome-informed strategy is essential for reducing global cancer disparities and improving outcomes in vulnerable populations. Full article

The convergence of artificial intelligence (AI) and nanomedicine has transformed cancer vaccine development, particularly in optimizing RNA-loaded lipid nanoparticles (LNPs). Stability and targeted delivery are major obstacles to the clinical translation of promising RNA-LNP vaccines for cancer immunotherapy. This systematic review analyzes the AI’s impact on LNP engineering through machine learning-driven predictive models, generative adversarial networks (GANs) for novel lipid design, and neural network-enhanced biodistribution prediction. AI reduces the therapeutic development timeline through accelerated virtual screening of millions of lipid combinations, compared to conventional high-throughput screening. Furthermore, AI-optimized LNPs demonstrate improved tumor targeting. GAN-generated lipids show structural novelty while maintaining higher encapsulation efficiency; graph neural networks predict RNA-LNP binding affinity with high accuracy vs. experimental data; digital twins reduce lyophilization optimization from years to months; and federated learning models enable multi-institutional data sharing. We propose a framework to address key technical challenges: training data quality (min. 15,000 lipid structures), model interpretability (SHAP > 0.65), and regulatory compliance (21CFR Part 11). AI integration reduces manufacturing costs and makes personalized cancer vaccine affordable. Future directions need to prioritize quantum machine learning for stability prediction and edge computing for real-time formulation modifications. Full article

Primary and secondary immunodeficiencies comprise a wide array of illnesses marked by immune system abnormalities, resulting in heightened vulnerability to infections, autoimmunity, and cancers. Notwithstanding progress in diagnostic instruments and an enhanced comprehension of the underlying pathophysiology, delayed diagnosis and underreporting persist as considerable obstacles. The implementation of artificial intelligence into clinical practice has surfaced as a viable method to enhance early detection, risk assessment, and management of immunodeficiencies. Recent advancements illustrate how artificial intelligence-driven models, such as predictive algorithms, electronic phenotyping, and automated flow cytometry analysis, might enable early diagnosis, minimize diagnostic delays, and enhance personalized treatment methods. Furthermore, artificial intelligence-driven immunopeptidomics and phenotypic categorization are enhancing vaccine development and biomarker identification. Successful implementation necessitates overcoming problems associated with data standardization, model validation, and ethical issues. Future advancements will necessitate a multidisciplinary partnership among physicians, data scientists, and governments to effectively use the revolutionary capabilities of artificial intelligence, therefore ushering in an age of precision medicine in immunodeficiencies. Full article

The generation of memory CD8⁺ T cells is essential for establishing protective T cell immunity against pathogens and cancers. However, the cellular and molecular mechanisms underlying memory CD8⁺ T cell formation remain incompletely understood. Reliance on specific pathogen-free (SPF) models, characterized by restricted microbial exposure, may limit our understanding of physiologically relevant immune memory development. This study reveals that CD1d-restricted NKT cells regulate central memory T cell (TCM) generation exclusively in a microbe-rich (“dirty”) environment. Under non-SPF housing, CD1d⁺/⁻ and Ja18⁺/⁻ mice exhibited enhanced TCM formation compared to NKT-deficient controls (CD1d⁻/⁻/Ja18⁻/⁻), demonstrating that microbial experience is required for NKT-mediated TCM regulation. Mechanistically, CD1d-restricted NKT cells increased IL-15Rα expression on CD4⁺ T cells in CD1d⁺/⁻ mice, potentiating IL-15 trans-presentation and thereby activating the IL-15/pSTAT5/Eomes axis critical for TCM maintenance. Functional validation through adoptive transfer of CFSE-labeled OT-1 memory cells revealed an NKT cell-dependent survival advantage in CD1d⁺/⁻ hosts. This provides direct evidence that microbiota-experienced niches shape immune memory. Collectively, these findings establish CD1d-restricted NKT cells as physiological regulators of TCM generation and suggest their potential utility as vaccine adjuvants to enhance protective immunity. Full article

The protein p53, often referred to as the “guardian of the genome,” is essential for preserving cellular balance and preventing cancerous transformations. As one of the most commonly altered genes in human cancers, its impaired function is associated with tumor initiation, development, and resistance to treatment. Exploring the diverse roles of p53, which include regulating the cell cycle, repairing DNA, inducing apoptosis, reprogramming metabolism, and modulating immunity, provides valuable insights into cancer mechanisms and potential treatments. This review integrates recent findings on p53′s dual nature, functioning as both a tumor suppressor and an oncogenic promoter, depending on the context. Wild-type p53 suppresses tumors by inducing cell cycle arrest or apoptosis in response to genotoxic stress, while mutated variants often lose these functions or gain novel pro-oncogenic activities. Emerging evidence highlights p53′s involvement in non-canonical pathways, such as regulating tumor microenvironment interactions, metabolic flexibility, and immune evasion mechanisms. For instance, p53 modulates immune checkpoint expression and influences the efficacy of immunotherapies, including PD-1/PD-L1 blockade. Furthermore, advancements in precision diagnostics, such as liquid biopsy-based detection of p53 mutations and AI-driven bioinformatics tools, enable early cancer identification and stratification of patients likely to benefit from targeted therapies. Therapeutic strategies targeting p53 pathways are rapidly evolving. Small molecules restoring wild-type p53 activity or disrupting mutant p53 interactions, such as APR-246 and MDM2 inhibitors, show promise in clinical trials. Combination approaches integrating gene editing with synthetic lethal strategies aim to exploit p53-dependent vulnerabilities. Additionally, leveraging p53′s immunomodulatory effects through vaccine development or adjuvants may enhance immunotherapy responses. In conclusion, deciphering p53′s complex biology underscores its unparalleled potential as a biomarker and therapeutic target. Integrating multi-omics analyses, functional genomic screens, and real-world clinical data will accelerate the translation of p53-focused research into precision oncology breakthroughs, ultimately improving patient outcomes. Full article

Cancer remains a major cause of mortality worldwide, driven by complex molecular mechanisms that promote metastasis and resistance to therapy. Receptor for hyaluronan-mediated motility (RHAMM) has emerged as a multifunctional regulator in cancer, contributing to cell motility, invasion, proliferation, and fibrosis. In addition to being regulated by non-coding RNAs (ncRNAs), including miRNAs, lncRNAs, and circRNAs, RHAMM serves as a promising therapeutic target. Recent developments in RHAMM-targeted strategies include function-blocking peptides (e.g., NPI-110, NPI-106, and P15-1), hyaluronan (HA) oligomers, and anti-RHAMM antibodies, all shown to modulate tumor stroma and suppress tumor invasiveness. Importantly, RHAMM-targeted peptide vaccines, such as the RHAMM-R3 epitope, have demonstrated immunogenicity and anti-leukemia efficacy in both pre-clinical and early clinical studies, suggesting their potential to elicit specific CD8⁺ T-cell responses and enhance graft-versus-leukemia effects. This review summarizes the intricate roles of RHAMM in cancer progression, its modulation by ncRNAs, and the translational promise of novel RHAMM-targeting approaches, providing insights into future directions for precision cancer therapy. Full article

Cervical cancer remains a significant global public health challenge, with human papillomavirus (HPV) as its primary cause. In response, the World Health Organization (WHO) launched a global strategy to eliminate cervical cancer by 2030 and, in its 2022 position paper, recommended a single-dose vaccination schedule. The objective of this review is to critically examine the current HPV vaccination landscape in China, including vaccination policies, immunization schedules, supply–demand dynamics, and the feasibility of transitioning to a single-dose regimen. By synthesizing recent developments in HPV virology, epidemiology, vaccine types, and immunization strategies, we identify both opportunities and barriers unique to the Chinese context. Results indicate that China primarily adheres to a three-dose vaccination schedule, with an optional two-dose schedule for girls aged 9–14, leaving a notable gap compared to the most recent WHO recommendation. The high prevalence of HPV types 52 and 58 contributes to a distinct regional infection pattern, underscoring the specific need for nine-valent vaccines tailored to China’s epidemiological profile. Despite the growing demand, vaccine supply remains inadequate, with an estimated annual shortfall of more than 15 million doses. This issue is further complicated by strong public preference for the nine-valent vaccine and the relatively high cost of vaccination. Emerging evidence supports the comparable efficacy and durable protection of a single-dose schedule, which could substantially reduce financial and logistical burdens while expanding coverage. This review advocates for the adoption of a simplified single-dose regimen, supported by catch-up strategies for older cohorts and the integration of HPV vaccination into China’s National Immunization Program (NIP). Sustained investment in domestic vaccine development and centralized procurement of imported vaccines may also possibly alleviate supply shortage. These coordinated efforts are critical for strengthening HPV-related disease prevention and accelerating China’s progress toward the WHO’s cervical cancer elimination targets. Full article

Outer-membrane vesicles (OMVs), naturally secreted by Gram-negative bacteria, have gained recognition as a versatile platform for the development of next-generation vaccines. OMVs are essential contributors to bacterial pathogenesis, horizontal gene transfer, cellular communication, the maintenance of bacterial fitness, and quorum sensing. Their intrinsic immunogenicity, adjuvant properties, and scalability establish OMVs as potent tools for combating infectious diseases and cancer. Recent advancements in genetic engineering and biotechnology have further expanded the utility of OMVs, enabling the incorporation of multiple epitopes and antigens from diverse pathogens. These developments address critical challenges such as antigenic variability and co-infections, offering broader immune coverage and cost-effective solutions. This review explores the unique structural and immunological properties of OMVs, emphasizing their capacity to elicit robust immune responses. It critically examines established and emerging engineering strategies, including the genetic engineering of surface-displayed antigens, surface conjugation, glycoengineering, nanoparticle-based OMV engineering, hybrid OMVs, and in situ OMV production, among others. Furthermore, recent advancements in preclinical research on OMV-based vaccines, including synthetic OMVs, OMV-based nanorobots, and nanodiscs, as well as emerging isolation and purification methods, are discussed. Lastly, future directions are proposed, highlighting the potential integration of synthetic biology techniques to accelerate research on OMV engineering. Full article

Circular RNA (CircRNA) is a single-stranded RNA arising from back splicing. CircRNAs interact with mRNA, miRNA, and proteins. These interactions regulate various life processes, including transcription, translation, cancer progression, anticancer drug resistance, and metabolism. Due to a lack of cap and poly(A) tails, circRNAs show exceptional stability and resistance to RNase degradation. CircRNAs exhibit dysregulated expression patterns in various cancers and influence cancer progression. Stability and regulatory roles in cancer progression make circRNAs reliable biomarkers and targets for the development of anticancer therapeutics. The dysregulated expression of circRNAs is associated with resistance to anticancer drugs. Enhanced glycolysis by circRNAs leads to resistance to anticancer drugs. CircRNAs have been known to regulate the response to chemotherapy drugs and immune checkpoint inhibitors. Exogenous circRNAs can encode antigens that can induce both innate and adaptive immunity. CircRNA vaccines on lipid nanoparticles have been shown to enhance the sensitivity of cancer patients to immune checkpoint inhibitors. In this review, we summarize the roles and mechanisms of circRNAs in anticancer drug resistance and glycolysis. This review discusses clinical applications of circRNA vaccines to overcome anticancer drug resistance and enhance the efficacy of immune checkpoint inhibitors. The advantages and disadvantages of circRNA vaccines are also discussed. Overall, this review stresses the potential value of circRNAs as new therapeutic targets and diagnostic/prognostic biomarkers for cancer Full article

Bovine papillomatosis, caused by a growing group of bovine papillomaviruses (BPVs), is a disease with benign proliferative lesions (papillomas) that may progress to malignancies due to immunological, environmental, or viral factors. This study investigated BPV type diversity in cattle from the Province Santo Domingo de Tsáchilas in Ecuador. Warty lesions were collected from 30 cattle across eight farms. Nucleic acids were extracted using a silicon dioxide-based method, and the partial L1 gene was amplified with PCR. DNA sequences were analyzed using maximum likelihood phylogenetics. Fifty-seven warty lesions yielded ten well-known BPV types: BPV1, BPV2, BPV4, BPV6, BPV8, BPV9, BPV10, BPV13, BPV14, and BPV42. Recently described viral types, BPV-CR2 from Costa Rica and BPV/BR-UEL08 from Brazil, were also detected, alongside a putative novel viral type, BPVEC2024-6-22.1—likely belonging to the genus Xipapillomavirus. This genus had the highest overall count. In contrast, Deltapapillomaviruses were found across all sampled farms. This study underscores BPV diversity in this localized region of Ecuador, and includes genotypes linked to cancers such as enzootic hematuria. The findings provide important epidemiological insights, contributing to vaccine development or immune therapy and improved disease management. Full article

Background: Cervical cancer is a major global health concern, causing approximately 350,000 deaths annually. It is also preventable through effective prevention and early detection. To facilitate elimination, the World Health Organization (WHO) set targets for HPV vaccination, screening, and treatment. Achieving these goals requires frameworks to monitor screening program performance. As many regions transition to HPV primary screening, a standardized Cervical Cancer Screening Cascade can track performance, identify gaps in follow-up, and optimize resource allocation. Methods: This paper introduces a structured cascade developed to monitor uptake, retention, and outcomes in HPV-based screening programs. The Cascade was created through collaboration between public health experts, clinicians, and researchers at the University of British Columbia (UBC), the Women’s Health Research Institute, and BC Cancer. Results: The Cascade outlines four phases: screening, triage, detection, and treatment. Each phase includes two substages: “uptake” and “results,” with an additional substage in screening (“invitation”). “Screening” assesses invitation effectiveness and participation. “Triage” tracks follow-up after a positive screen. “Detection” evaluates attendance at diagnostic appointments, and “Treatment” measures the treatment rate for those with precancerous lesions. Conclusions: The Cascade can guide emerging and existing HPV screening programs within Canada and other similarly resourced settings and serve as a benchmark tool for programs to assess their progress towards cervical cancer elimination. Full article

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with high recurrence rates even after curative resection and adjuvant chemotherapy. Although immunotherapeutic approaches, such as immune checkpoint blockade (ICB), have revolutionized the treatment of some solid tumor malignancies, this has not been the case for PDAC. Several characteristics of PDAC, including its distinctive desmoplastic tumor microenvironment (TME), intratumor heterogeneity, and poor antigenicity and immune cell infiltration, contribute to its dismal immunotherapeutic landscape. Cancer vaccines offer one approach to overcoming these barriers, particularly in the resectable or borderline resectable settings, where tumor burden is low and immunosuppression is less pronounced. Various vaccination platforms have been tested in the clinical setting, from off-the-shelf peptide-based vaccines (e.g., AMPLFIFY-201 study, where over 80% of participants exhibited T-cell and biomarker responses) to personalized neoantigen mRNA vaccine approaches (e.g., autogene cevumeran, with significant responders experiencing longer median recurrence-free survival (RFS)). The key considerations for enhancing the efficacy of vaccination include combinations with chemotherapy, radiotherapy, and/or ICBs, as well as selecting appropriate immunomodulators or adjuvants. Recent results suggest that with continued mechanistic advancement and novel therapeutic development, cancer vaccines may finally be poised for clinical success in PDAC. Full article

Oncoviruses, such as Epstein–Barr virus (EBV), human papillomavirus (HPV), and Kaposi sarcoma-associated herpesvirus (KSHV), have been widely discussed for their oncogenic risk. Initially, the oral cavity was disregarded. In recent years, orientation has shifted to the importance of the oral cavity and cancer-related issues via Handbook 19 titled “Oral Cancer Prevention” by the International Agency for Research on Cancer, the WHO Global Oral Health Status Report 2022, and multiple other actions focused on reducing the oversight of this neglected area. Oncoviruses play a significant role in oral cavity malignancies by establishing persistent infections, evading host immune responses, and inducing cellular transformation through the disruption of normal regulatory pathways. Molecular biology and microbiome research have advanced our understanding of the complex interplay between oncoviruses and oral microbiota, demonstrating how coinfections and dysbiosis can enhance viral oncogenic potential. These findings improve the understanding of virus-induced oral cancers and support the development of novel diagnostic and therapeutic strategies. This narrative review focuses on the relationship between oncoviruses and the oral cavity by focusing on how a specific virus triggers tumorigenesis for each of the described viruses and how it affects oral cavity cancer development. Finally, we describe recent advances and future perspectives including vaccines and/or treatment. Full article

Background/Objectives: Pancreatic cancer remains the fourth leading cause of cancer-related deaths. While peripheral blood-derived mature dendritic cell (mDC) vaccines have shown potential in eliciting anti-tumor immune responses, clinical efficacy has been limited. This study aimed to enhance the potency and scalability of DC-based immunotherapy by developing an allogeneic DC platform derived from CD34⁺ hematopoietic stem cells (HSCs), genetically engineered to overexpress CD93, CD40L, and CXCL13, followed by maturation and tumor antigen pulsing. Methods: Engineered DCs were generated from CD34⁺ HSCs and matured in vitro after lentiviral transduction of CD93, CD40L, and CXCL13. Tumor lysates were used for antigen pulsing. A scrambled-sequence control DC was used for comparison. In vitro assays were performed to assess T cell activation and tumor cell killing. In vivo efficacy was evaluated using orthotopic pancreatic tumors in BLT and PBMC-humanized NSG mice established with the MiaPaca-2 (MP2) cell line. Results: Engineered DCs significantly enhanced T cell activation and tumor-specific cytotoxicity in vitro compared to control DCs. Antigen pulsing further amplified immune activation. In vivo, treated humanized mice showed increased CD4⁺, CD8⁺, and NK cell frequencies in peripheral blood and within tumors, correlating with reduced tumor burden. Conclusions: Our data shows that the antigen-pulsed, engineered DCs have the potency to activate immune cells, which leads to a significant reduction in pancreatic tumors and therefore could potentially provide an effective therapeutic opportunity for the treatment of pancreatic cancer and other solid tumors. Full article

Liver cancer has high incidence and mortality rates worldwide, with hepatocellular carcinoma (HCC) being the main histological subtype, accounting for 90% of primary liver cancers. The high mutation rate of viruses combined with endoplasmic reticulum stress may lead to the occurrence of cancer. Hepatitis B virus (HBV) infection is one of the most important pathogenic factors of HCC. The carcinogenic mechanisms of HBV have been widely studied. Among these mechanisms, immune escape and vaccine escape caused by mutations in the HBV S gene have been reported in numerous studies of patients with chronic hepatitis B. In addition, pre-S1/S2 mutations and surface protein truncation mutations may activate multiple signaling pathways. This activation leads to the abnormal proliferation and differentiation of hepatocytes, thereby contributing to the development of HCC. This review aims to integrate the existing literature, summarize the common mutations in the HBV S gene region, and explore the related pathogenic mechanisms. Full article