Search Results (2,827)

The discovery of neoantigens and their application in cancer vaccines have brought about a paradigm shift in cancer immunotherapy, similar to the way in which immune checkpoint inhibitors redefined therapeutic strategies for cancer treatment. Early neoantigen vaccine approaches primarily focused on eliciting HLA class I-restricted CD8⁺ cytotoxic T lymphocyte (CTL) responses, whereas it has become clear that such strategies alone may be insufficient to establish durable and effective antitumor immunity. Increasing attention has therefore shifted toward HLA class II-restricted neoantigens (“helper neoantigens”) that activate tumor-specific CD4⁺ helper T cells. Recent studies have revealed that neoantigen-reactive CD4⁺ helper T cells play a central role in coordinating antitumor immune responses through dendritic cell licensing, thereby sustaining CD8⁺ CTL function, preventing T-cell exhaustion, and promoting the generation of long-lived memory T cells. These findings have highlighted the pivotal role of helper neoantigens in shaping vaccine efficacy. In this review, we discuss the mechanistic basis underlying the contribution of helper neoantigens to tumor immunity and highlight recent advances in the real-world application of helper neoantigen-based vaccine strategies. Full article

We report the first documented case of extreme, intact parathyroid hormone (PTH)-independent hypercalcemia mediated by a rare non-osteoclastic bone remodeling mechanism in a 65-year-old Puerto Rican woman, detected within 24 h of the second dose of the Moderna mRNA-1273 COVID-19 vaccine and leading to the diagnosis of high-risk biclonal IgA plasma cell myeloma (R-ISS Stage III). Peak serum calcium reached 17.4 mg/dL with concurrent hyperphosphatemia, normal lactate dehydrogenase (LDH), and without marrow osteoclasts or osteolytic lesions, findings inconsistent with classical cancer-associated hypercalcemia. Hypercalcemia resolved within eight days with supportive treatment alone, remaining durably normal nine months later. The temporal proximity to vaccination, together with the biochemical–histopathological profile, generates the hypothesis, without implying causation, that a vaccine-induced innate immune response triggered a rare inflammatory osteocytic perilacunar/canalicular remodeling. The biclonal gammopathy, Clone-1 (normal karyotype, CD33⁺, OCT-2⁺, MYC⁻, CD19⁺, PAX5⁻) and Clone-2 (complex high-risk karyotype, OCT-2⁻, MYC⁺low, CD19⁻), suggests epigenetic rather than genomic drivers in the predominant clone. This case proposes a novel mechanistic hypothesis for vaccine-associated hypercalcemia and generates testable questions that warrant prospective investigation. Full article

Oncogenic viruses contribute to approximately 20% of human cancers globally, with their impact falling disproportionately on populations in Sub-Saharan Africa. In this region, cervical cancer, hepatocellular carcinoma, endemic Burkitt lymphoma, and Kaposi sarcoma represent major causes of cancer-related morbidity and mortality, driven by persistent infection with human papillomavirus (HPV), hepatitis B and C viruses (HBV/HCV), Epstein–Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), and human T-lymphotropic virus-1 (HTLV-1). This review synthesizes current insights into the immunological mechanisms that underpin viral carcinogenesis in Africa, emphasizing how defective viral clearance, chronic immune activation, and immune evasion arise from the convergence of region-specific co-infections, host genetic diversity, and environmental exposures. We examine the mechanistic roles of HIV-associated CD4⁺ T cell depletion, malaria-induced perturbation of antiviral T cell immunity, helminth-driven T helper 2 polarization, and tuberculosis-associated inflammatory signaling in promoting viral persistence and malignant transformation. In addition, the influence of the extensive diversity of African human leukocyte antigens (HLA) and cytokine gene polymorphisms on antiviral immune responses and cancer susceptibility was discussed. We also assessed how virus-associated tumors establish profoundly immunosuppressive microenvironments characterized by impaired antigen presentation and the dominance of immune checkpoint pathways. Finally, we examined how gaps in vaccination, screening, and diagnostic capacity intersect with immunological vulnerability across Africa, contributing to the burden of infection-associated cancers. These challenges position Africa as a critical setting for developing targeted, genotype-inclusive public health interventions and reducing global cancer disparities through advances in immunoprevention and immunotherapy. Full article

Background: Human papillomavirus (HPV) continues to cause an estimated 4000 preventable cancer deaths each year in the United States. Given the prevalence of HPV-related disease and suboptimal vaccination rates, this study explores perceptions of HPV vaccination among HIV-negative females and females living with HIV in Tennessee. Methods: This prospective, observational qualitative study consisted of narrative interviews which were conducted with HIV-negative and HIV-positive participants, focusing on their perceptions of HPV and its vaccine. Interviews were conducted by phone, and the verbatim transcripts were inductively coded by three researchers. The inductive codes were then grouped into categories based on similarities which facilitated the emergence of themes. Results: A total of 40 participants were interviewed between July 2024 and December 2024. Narrative analysis revealed three themes: (1) “I had never heard of it until I saw the flier.” Gaps in Understanding of HPV and Its Health Implications, (2) Navigating Adolescent Health Decisions and Emotional Influence, and (3) Barriers to Uptake—Skepticism, Trust, and the Need for Tailored Information. Two subthemes emerged: Cohort-Specific Skepticism, and Parental Influence and Communication Gaps. Conclusions: This study revealed significant gaps in HPV knowledge and vaccination uptake among HIV-negative women and women living with HIV in Tennessee. Provider communication was key to vaccine decisions, but clear recommendations were often missed in clinical encounters. Full article

Therapeutic cancer vaccines are designed to initiate tumor-specific immunity, yet their clinical success depends not only on antigen selection but also on the capacity to overcome the profoundly suppressive tumor microenvironment. Within tumors, abnormal vasculature, hypoxia, nutrient competition, acidic pH, and suppressive myeloid and stromal cells collectively constrain antigen presentation, T-cell priming, trafficking, and effector function, often converting otherwise immunogenic vaccination into an ineffective immune stimulus. Recent advances in neoantigen discovery, dendritic cell engineering, and nucleic acid-based vaccine platforms have improved the precision of antigen delivery, but these gains remain insufficient unless vaccine-induced responses can be sustained and executed within the hostile metabolic and immunologic landscape of the tumor niche. In this context, the tumor microenvironment is not merely a barrier to be overcome, but an active determinant of vaccine outcome that shapes immune editing, promotes exhaustion, and limits intratumoral expansion of cytotoxic lymphocytes. Accordingly, the most promising therapeutic strategies now combine vaccination with checkpoint blockade, radiotherapy, stromal remodeling, or metabolic reprogramming to recondition the tumor ecosystem and permit productive antitumor immunity. Here, we discuss how tumor microenvironmental constraints govern vaccine performance, review emerging platform technologies, and outline combinatorial strategies aimed at converting immune priming into durable tumor control. Full article

Virus-based cancer therapy (virotherapy) is currently being researched as a novel form of immunotherapy and has already entered the clinical application phase. Among various types of virotherapy, oncolytic virotherapy involves infecting tumors with tumor-selective viruses, such as herpes simplex virus, adenoviruses, and vaccinia virus, and utilizing their replicative capacity to induce cell destruction within tumors. In addition, this therapy aims to enhance tumor immunity by changing the tumor microenvironment through viral infection. Genetic deletion in viruses is used to reduce their virulence and confer tumor selectivity, while the expression of foreign genes is utilized to enhance antitumor effects. Oncolytic viruses for head and neck cancer (HNC) are administered locally or systemically and are sometimes used as adjuvant therapy or in combination with immune checkpoint inhibitors. Another form of virotherapy involves non-replicating viruses, which are used to produce antitumor cytokines or as cancer vaccines expressing tumor antigens. Research on the efficacy of cancer vaccines in preventing postoperative recurrence is currently underway. A number of challenges have yet to be overcome for further advances in virotherapy, including the efficient delivery of viruses to tumor cells, avoiding viral inactivation in the bloodstream, ensuring efficient replication of the virus, and enhancing antitumor immunity. The development of effective strategies based on the findings of clinical studies will lead to improvements in virotherapy for HNC. Full article

This review provides an updated and comprehensive assessment of the current literature on quinoa (Chenopodium quinoa Willd.) saponins, with particular emphasis on pharmacological effects. Quinoa (Chenopodium quinoa Willd.) is an annual plant native to South America. Quinoa seeds are characterized by high nutritional value and are rich in proteins, lipids, carbohydrates, minerals, and saponins. Saponins are found in quinoa seeds and impart a bitter taste, which is why they are typically removed before seed consumption. Saponins have been characterized as antinutritional agents, but in recent years they have been investigated for their pharmaceutical applications. Protocols have been developed for the extraction of saponins from seeds, such as conventional solid–liquid extraction (maceration), ultrasound-assisted extraction, microwave-assisted extraction, enzyme-assisted extraction, and pressurized liquid extraction. Ultrasound-assisted extraction and microwave-assisted extraction are considered the most suitable methods for quinoa saponins. Quinoa saponins have shown promise as vaccine adjuvants. Furthermore, they have demonstrated direct anticancer activity, inducing apoptosis and inhibiting the proliferation of breast and colon cancer cells. In general, saponins can induce hemolysis at high concentrations through membrane disruption, primarily via lipid solubilization or pore formation. However, hemolytic activity varies significantly among different saponins and depends on their chemical structure and concentration. In vivo, they have not recorded adverse side effects at doses below 50 mg/kg body weight per day. More than 40 triterpenoid saponins, mainly derived from oleanolic acid, ederagenin, phytolaccagenic acid, and sergianic acid, have been identified in quinoa. Overall, although quinoa saponins have traditionally been considered antinutritional compounds, accumulating evidence indicates that they possess promising pharmacological properties, particularly as anticancer agents. Full article

Inhalable ribonucleic acid (RNA) nanomedicines are emerging as versatile therapeutics for respiratory diseases and pulmonary metastases, enabling localized delivery of messenger RNA (mRNA), small interfering RNA (siRNA), antisense oligonucleotides, microRNA (miRNA) mimics, self-amplifying RNA, and genome-editing systems. This review synthesizes the available evidence and argues that the field has moved beyond asking whether RNA can reach the lungs. The more consequential translational question is whether RNA cargo, nanocarrier, excipients, manufacturing process, inhalation device, and pulmonary target cell can be integrated into a reproducible therapeutic product. Current research demonstrates progress in disease-corrective mRNA expression, silencing of inflammatory and fibrotic pathways, mucosal vaccination, antiviral therapy, and localized cancer treatment, alongside advances in ionizable lipid nanoparticles, lipid–polymer hybrids, chitosan and polyethyleneimine (PEI) polyplexes, dendrimers, peptide carriers, biomimetic systems, and dry-powder formulations. Translational maturity, however, remains uneven. Many studies demonstrate carrier feasibility, reporter expression, or preclinical activity, whereas fewer establish device-compatible aerosolization, preservation of RNA integrity during processing, traversal of pulmonary barriers, target-cell engagement, repeat-dose tolerability, and clinically meaningful benefit. Development should therefore be target-defined, analytically gated, device-specific, and outcome-centered. Inhalable RNA nanomedicines are best understood as integrated pulmonary products whose success depends on preserving RNA function throughout manufacturing, aerosolization, post-deposition barrier navigation, intracellular delivery, and disease-relevant pharmacodynamic activity. Full article

Background: India accounts for one-fifth of global cervical cancer deaths, yet Human Papillomavirus (HPV) vaccination coverage remains low despite the World Health Organization (WHO) recommendations to initiate vaccination at age 9. With the national HPV vaccination campaign in 2026 and its approval for integration into India’s Universal Immunization Programme (UIP), strengthening physician knowledge, beliefs, and confidence in recommending the vaccine is critical. Methods: In 2023, the American Cancer Society and Cancer Foundation of India catalyzed two national medical societies, the Federation of Obstetric and Gynaecological Societies of India and the Indian Academy of Pediatrics, to educate physicians on HPV vaccination using a train-the-trainer (ToT) model. A mixed-methods evaluation, using the RE-AIM Framework, included pre- and post-training surveys assessing changes in knowledge, beliefs, confidence, and intent, as well as monthly engagement surveys and project reports analyzed using descriptive and inferential statistics. A fidelity assessment evaluated consistency of training delivery. Twenty in-depth interviews explored physician reactions and implementation of learnings, analyzed using a rapid approach. Results: A total of 18,206 physicians were trained. The post-training respondent group demonstrated higher HPV vaccination knowledge scores and more favorable responses in confidence, beliefs, and intent than the pre-training respondent group. The fidelity assessment demonstrated consistent delivery overall, with some variability in role play facilitation. Interviews highlighted increased physician confidence, peer knowledge sharing, and community engagement following the training. Medical societies reported strong program adoption and plans for continued efforts. Conclusions: A ToT physician training cascaded through medical societies is a feasible strategy to prepare physicians to recommend the HPV vaccine and address parental concerns at scale. Full article

Background: Although cervical cancer is a highly preventable malignancy, Romania continues to report critical mortality rates. This paradox is largely attributable to the suboptimal implementation of clinical guidelines and a passive, “opt-in” administrative framework. This cross-sectional study investigates the cognitive and behavioural determinants—specifically, human papillomavirus (HPV) knowledge, institutional trust in healthcare systems, and digital misinformation exposure—that modulate female attitudes toward HPV immunisation. Methods: An observational cross-sectional study was conducted between December 2025 and March 2026 across four obstetrics and gynaecology clinics. Data were collected via digital questionnaires administered to adult female patients aged 18 to 65 years. The assessment tool evaluated four primary domains: HPV knowledge, perceived vaccine safety, immunisation intention, and the degree of exposure to social media misinformation. Results: The cohort demonstrated a substantially low vaccination rate (28.6%). Statistical analysis elucidated significant positive correlations between HPV knowledge, trust in health authorities, and vaccination intention. Furthermore, reliance on official information sources strongly correlated with perceived vaccine safety. Conversely, exposure to negative online content exhibited a weak negative association with knowledge levels, yet it did not directly influence vaccination intention. Conclusions: Health literacy and institutional trust emerge as fundamental pillars for HPV vaccine acceptance. To overcome patient vaccine hesitancy, the national healthcare system must initiate a strategic paradigm shift, prioritising the neutralization of digital misinformation and transitioning from a passive model to a proactive, “opt-out” infrastructure. Full article

Background/Objectives: SARS-CoV-2, influenza viruses, and respiratory syncytial virus (RSV) remain major causes of adult hospitalizations, but contemporary comparative data are limited. This study compared the epidemiological characteristics, clinical presentation, and outcomes of adults hospitalized with these infections during the 2025/2026 epidemic season in Poland. Methods: We conducted a retrospective multicenter study of consecutive adults hospitalized with laboratory-confirmed COVID-19, influenza, or RSV infection between September 2025 and April 2026. Demographic characteristics, comorbidities, vaccination status, clinical features, laboratory findings, and outcomes were analyzed. Independent predictors of in-hospital mortality were identified using multivariable logistic regression. Results: The study included 604 patients: 255 with COVID-19, 314 with influenza, and 35 with RSV infection. Distinct seasonal patterns were observed, with COVID-19 peaking in autumn, influenza in winter, and RSV in early spring. Most hospitalized patients were elderly and unvaccinated. RSV patients were older, more frequently affected by multimorbidity, ischemic heart disease, and cancer, and showed the greatest respiratory impairment, including the highest rates of hypoxemia and pneumonia. Influenza was characterized by more frequent fever, headache, and myalgia. Despite lower pneumonia rates, COVID-19 was associated with the highest in-hospital mortality (13.7%) and remained an independent predictor of death (aOR = 3.23, 95%CI: 1.68–6.22). Antibiotic use was common across all cohorts (62–77%). Conclusions: COVID-19 remained associated with the highest mortality among hospitalized adults, whereas RSV contributed substantially to respiratory morbidity in older individuals. These findings support improved vaccination uptake, continued surveillance, hospital preparedness, and antimicrobial stewardship. Full article

RNA vaccines have emerged as an attractive platform for treating infectious diseases, cancer immunotherapy, and personalized medicine; however, their clinical success depends on multiple factors, including efficient, stable, and scalable delivery systems. Because RNA molecules are highly sensitive to factors such as enzymatic degradation, oxidation, poor cellular uptake, and limited endosomal escape, nanocarrier platforms play essential roles in protecting RNA cargo and enabling effective intracellular delivery. The biological performance of RNA nanocarriers depends on efficient cellular uptake, endosomal escape, intracellular RNA delivery, biodistribution, and immune modulation. Comparative assessment emphasizes that lipid nanoparticles remain the most clinically mature approach, while nanostructured lipid carriers, polymeric systems, and exosome-based nanocarriers provide multiple benefits for stability, targeted delivery, biocompatibility, and/or controlled release. Translational challenges involving GMP manufacturing, batch reproducibility, regulatory expectations, and scale-up are considered critical for effective nano-based RNA vaccine delivery and are elaborated in this review. Emerging advances such as pKa-tuned ionizable lipids, ligand-targeted systems, stimuli-responsive nanocarriers, circular and self-amplifying RNA platforms, artificial intelligence-guided formulation design, and needle-free delivery technologies may further expand the safety, accessibility, and therapeutic potential of RNA vaccines. In this review, we highlight next-generation nanocarrier systems for RNA vaccines, with an emphasis on novel nanocarrier RNA vaccine delivery systems. Additionally, we evaluate stability engineering approaches that currently limit global vaccine distribution and the future of the nanocarrier platforms for RNA vaccines. Full article

Breast cancer remains one of the most prevalent malignancies affecting women worldwide and continues to be a leading cause of cancer-related morbidity and mortality. Patients may present with either localized or advanced disease, with clinical outcomes increasingly influenced by molecular subtype and genetic profile. This review highlights the key genetic factors involved in breast cancer, current diagnostic and therapeutic strategies, and promising emerging approaches that may shape future clinical management. Breast cancer diagnosis typically involves clinical breast examination, imaging techniques such as mammography and ultrasound, and confirmatory biopsies. Genetic mutations in specific genes are strongly linked to the development, progression, and metastasis of the disease. Treatment options for localized breast cancer continue to include surgery (lumpectomy or mastectomy) and radiotherapy, combined with systemic therapies tailored to tumor biology, such as endocrine therapy, human epidermal growth factor receptor 2 (HER2)-targeted therapy, and cyclin-dependent kinase (CDK)4/6 inhibitors. For advanced or metastatic breast cancer, recent therapeutic advances include the use of immunotherapy (e.g., immune checkpoint inhibitors), Poly (ADP-ribose) polymerase (PARP) inhibitors for Breast Cancer gene (BRCA)-mutated cancers, antibody–drug conjugates, and novel targeted agents, which have significantly improved patient outcomes in selected populations. Recent findings in breast cancer genetics have highlighted the critical role of germline and somatic mutations, particularly in genes such as BRCA1, BRCA2, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), and TP53, in driving tumor initiation, progression, and therapeutic response. Molecular profiling and next-generation sequencing technologies have enabled more precise tumor classification and facilitated the development of personalized treatment strategies. Despite these advances, treatment resistance and disease recurrence remain major challenges, particularly in aggressive subtypes such as triple-negative breast cancer. Consequently, ongoing research is exploring alternative and complementary approaches, including nanotechnology-based drug delivery systems, gene editing techniques such as clustered regularly interspaced short palindromic repeats-Cas9 (CRISPR-associated protein 9) (CRISPR-Cas9), cancer vaccines, and the integration of traditional and plant-derived compounds. These strategies aim to enhance therapeutic efficacy, reduce systemic toxicity, and overcome resistance mechanisms. Full article

Vaccinations are a cornerstone of primary prevention in pediatric otolaryngology and play a critical role in reducing the burden of pediatric infectious diseases, particularly acute otitis media (AOM) and HPV-related infections. The introduction and widespread use of pneumococcal conjugate vaccines (PCVs) have been associated with substantial changes in the epidemiology of pediatric AOM, particularly through reductions in vac-cine-serotype disease and complicated forms, while contributing to changes in pathogen distribution with an increased role of non-vaccine serotypes and non-pneumococcal bac-teria, requiring continuous epidemiological surveillance. Prophylactic human papillomavirus (HPV) vaccination in adolescents and young adults effectively prevents oral infection with vaccine-type high-risk HPV, a necessary step in the pathogenesis of HPV-related oropharyngeal carcinoma. Clinical and epidemiological studies demonstrate robust antibody responses and significant reductions in oral HPV prevalence among vaccinated individuals. Although direct evidence of a reduction in oropharyngeal cancer incidence is not yet available, vaccination may consequently reduce the future burden of HPV-related oropharyngeal cancers. Long-term surveillance remains essential to confirm this potential benefit. Barriers to optimal vaccine coverage include unequal access, incomplete vaccination uptake, and limited awareness of HPV-related oral disease. In conclusion, vaccinations provide direct and clinically relevant benefits in pediatric otolaryngology by reducing recurrent AOM, severe complications and surgical interventions. HPV vaccination also reduces vaccine-type oral HPV infection and may consequently contribute to reducing the future burden of HPV-related oropharyngeal cancers. Achieving high vaccination coverage, coupled with continuous epidemiological monitoring, is essential to maximize individual and public health benefits and to inform the development of vaccines with broader serotype coverage. Full article

Immune checkpoint inhibitors and antibody–drug conjugates have rapidly expanded treatment options for gynecologic malignancies, although the magnitude of benefit varies substantially across tumor types and biomarker-defined populations. This narrative review summarizes the biologic rationale, predictive biomarkers, pivotal clinical trials, regulatory approvals, guideline-supported strategies, and emerging directions for immune checkpoint blockade and antibody–drug conjugates in endometrial, cervical, and ovarian cancers. In endometrial cancer, molecular classification and mismatch repair status have transformed treatment selection, with PD-1 or PD-L1 blockade now integrated into first-line chemoimmunotherapy and recurrent disease management. HER2-directed and TROP-2-directed antibody–drug conjugates are also emerging as biomarker-directed strategies. In cervical cancer, human papillomavirus-driven tumor biology, PD-L1 expression, and tissue factor expression support the use of checkpoint inhibitors, antibody–drug conjugates, and therapeutic vaccine approaches across locally advanced and recurrent or metastatic settings. In ovarian cancer, single-agent checkpoint blockade has shown limited activity in unselected populations, but recent advances include biomarker-selected chemoimmunotherapy in platinum-resistant disease and clinically meaningful activity of folate receptor alpha-directed and HER2-directed antibody–drug conjugates. Across gynecologic cancers, key challenges include refining predictive biomarkers, optimizing sequencing after prior immunotherapy exposure, managing overlapping toxicities, and designing trials that enrich for biologically responsive subgroups. Future progress will depend on integrating molecular classification, immune contexture, ADC target expression, and patient-specific clinical factors into treatment selection. Full article