Search Results (891)

Iron oxide nanoparticles (IONPs) have emerged as key materials in magnetic hyperthermia (MH), a minimally invasive cancer therapy capable of selectively inducing apoptosis, ferroptosis, and other cell death pathways while sparing surrounding healthy tissue. This review synthesizes advances in the design, functionalization, and biomedical application of magnetic nanoparticles (MNPs) for MH, highlighting strategies to optimize heating efficiency, biocompatibility, and tumor targeting. Key developments include tailoring particle size, shape, and composition; doping with metallic ions; engineering multicore nanostructures; and employing diverse surface coatings to improve colloidal stability, immune evasion, and multifunctionality. We discuss preclinical and clinical evidence for MH, its integration with chemotherapy, radiotherapy, and immunotherapy, and emerging theranostic applications enabling simultaneous imaging and therapy. Special attention is given to the role of MNPs in immunogenic cell death induction and metastasis prevention, as well as novel concepts for circulating tumor cell capture. Despite promising results in vitro and in vivo, clinical translation remains limited by insufficient tumor accumulation after systemic delivery, safety concerns, and a lack of standardized treatment protocols. Future progress will require interdisciplinary innovations in nanomaterial engineering, active targeting technologies, and real-time treatment monitoring to fully integrate MH into multimodal cancer therapy and improve patient outcomes. Full article

Background and objectives: Clinical laboratory analyses are essential for diagnosing and treating allergic diseases mediated by immunoglobulin E (IgE). Identifying the sources of sensitivity, subject to regional variations, enables the implementation of effective management strategies, such as prevention and immunotherapy. Through a cross-sectional study, this study aimed to determine the sensitivity profile to aeroallergens (latent class) and their correlation with age, sex, and season in the population sampled. Methods: The purpose was to map the concentrations of specific IgE serum levels linked to the most prevalent allergens, considering variations related to age, specific IgE levels, and seasons of the year through a cross-sectional study. Results: The 995 reports of specific IgE tests analyzed were clustered into six aeroallergen categories and were predominantly composed of female individuals (57.1%). The most prevalent age group was younger than 18 (56.5%), and most exams were performed in the spring (27.7%). The aeroallergen category ‘grass’ significantly correlated with sex and age, indicating that men have a 65% greater probability of having high levels of specific IgE as a response to this allergen, and age is related to higher IgE levels. Latent class analysis identified an optimal three-class solution for specific IgE sensitization patterns: Class 1: Moderate Sensitization; Class 2: Low Sensitization; and Class 3: High Sensitization. Conclusion: The present study highlights the importance of knowing the local aeroallergen profile for early diagnosis and prevention of allergic diseases, emphasizing the relevance of the allergen category related to the age and sex of the individuals. Full article

Recent progress in tumor immunotherapy highlights the important role of the immune system in combating various cancers. Traditionally designed to protect against infectious diseases, vaccines are now being adapted to stimulate immune responses against tumor-specific neoantigens. Both preclinical studies and clinical trials have explored innovative approaches for identifying neoantigens and optimizing vaccine design, advancing the field of personalized oncology. Among these, DNA-based vaccines have become a particularly attractive approach for cancer immunotherapy. This evolution has been driven by improvements in molecular biology techniques, including more precise methods for detecting tumor-specific mutations, computational tools for predicting immunogenic antigens, and novel platforms for delivering nucleic acid vaccines. Personalized DNA vaccines are typically developed through a complex, multi-step process that involves sequencing a patient’s tumor, computational analysis to identify potential targets, and custom vaccine production. In this review, we examine the use of both shared tumor antigens and individualized neoantigens in cancer vaccine development. We outline strategies for neoantigen identification that provide insights into tumor-specific alterations. Furthermore, we highlight recent advances in DNA vaccine technologies, address the current limitations facing cancer vaccines, propose strategies to overcome these challenges, and consider key clinical and technical factors for successful implementation. Full article

Immunogenic cell death (ICD) is a specialized form of cell death that triggers antitumor immune responses. In tumors, ICD promotes the release of tumor-associated and tumor-specific antigens, thereby reshaping the immune microenvironment, restoring antitumor immunity, and facilitating tumor eradication. However, the regulatory mechanisms of ICD and its immunological effects vary across tumor types, and a comprehensive understanding remains limited. We systematically analyzed the expression of 34 ICD-related regulatory genes across 33 tumor types. Differential expression at the RNA, copy number variation (CNV), and DNA methylation levels was assessed in relation to clinical features. Associations between patient survival and RNA expression, CNVs, single-nucleotide variations (SNVs), and methylation were evaluated. Patients were stratified into immunological subtypes and further divided into high- and low-risk groups based on optimal prognostic models built using a machine learning framework. We explored the relationships between ICD-related genes and immune cell infiltration, stemness, heterogeneity, immune scores, immune checkpoint and regulatory genes, and subtype-specific expression patterns. Moreover, we examined the influence of immunotherapy and anticancer immune responses, applied three machine learning algorithms to identify prognostic biomarkers, and performed drug prediction and molecular docking analyses to nominate therapeutic targets. ICD-related genes were predominantly overexpressed in ESCA, GBM, KIRC, LGG, PAAD, and STAD. RNA expression of most ICD-related genes was associated with poor prognosis, while DNA methylation of these genes showed significant survival correlations in LGG and UVM. Prognostic models were successfully established for 18 cancer types, revealing intrinsic immune regulatory mechanisms of ICD-related genes. Machine learning identified several key prognostic biomarkers across cancers, among which NT5E emerged as a predictive biomarker in head and neck squamous cell carcinoma (HNSC), mediating tumor–immune interactions through multiple ligand–receptor pairs. This study provides a comprehensive view of ICD-related genes across cancers, identifies NT5E as a potential biomarker in HNSC, and highlights novel targets for predicting immunotherapy response and improving clinical outcomes in cancer patients. Full article

Pleural Mesothelioma (PM) remains a challenging malignancy associated with asbestos exposure and characterized by poor prognosis. This review aims to consolidate recent findings on the efficacy of perioperative therapies encompassing chemotherapy, surgery, and emerging immunotherapy strategies. Current management strategies debate the role of surgery in early-stage patients, particularly due to the limited success of solitary treatment modalities and significant rates of postoperative complications. Retrospective studies indicate that multimodal treatment, incorporating surgical resection with perioperative chemotherapy, can enhance overall survival (OS), especially in favorable prognostic subsets. However, significant randomized trials, notably the MARS and MARS 2 trials, revealed that the addition of aggressive surgical strategies like extrapleural pneumonectomy (EPP) did not confer survival benefits and was accompanied by heightened morbidity. In light of persistent challenges, integrating perioperative chemotherapy—primarily with platinum-based regimens—has shown improved disease control outcomes. Neoadjuvant chemotherapy permits real-time assessment of tumor responsiveness, providing valuable clinical insights for surgical candidacy. The role of immunotherapy, particularly immune checkpoint inhibitors (ICIs), is also under active exploration, with preliminary results suggesting promising activity and manageable safety profiles. In conclusion, while current protocols primarily recommend surgery for a select group of patients, ongoing investigations into neoadjuvant approaches, adjuvant therapies, and novel immunotherapeutic strategies are crucial for developing effective, personalized treatment paradigms for PM. Future efforts should prioritize clinical trials that integrate these therapies within a structured multidisciplinary approach to optimize patient outcomes. Full article

Gastrointestinal (GI) lymphomas are a diverse group of extranodal non-Hodgkin lymphomas primarily affecting the stomach, small intestine, and colon. They present with non-specific symptoms such as abdominal pain, weight loss, or GI bleeding, making early diagnosis challenging. Histologic subtypes vary, with mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBCL) being the most common. Diagnosis involves endoscopic evaluation with biopsy, cross-sectional imaging, and often PET-CT. Management is subtype-dependent, including antibiotics for H. pylori-associated MALT lymphoma, chemotherapy, immunotherapy, and occasionally surgery. A multidisciplinary approach is essential for optimal outcomes. Core Tip: Gastrointestinal lymphomas are rare but clinically significant malignancies with variable presentations. Accurate diagnosis and tailored treatment based on the histologic subtype and site are critical, requiring close collaboration among gastroenterologists, pathologists, oncologists, and radiologists. Full article

This review covers issues related to the characteristics, diagnosis, and treatment of colorectal cancer (CRC). It discusses traditional methods of treating colorectal cancer, including surgery, chemotherapy, and radiotherapy, as well as modern approaches, including targeted therapies, immunotherapy, and innovative gene therapy strategies. Particular attention is paid to the identification of molecular subtypes of CRC, which has revolutionized treatment in advanced stages of the disease and contributed to improved patient survival. The role of biomarkers, including liquid biopsy, in diagnosis, therapy monitoring, and treatment response assessment is emphasized. The potential of artificial intelligence in planning and optimizing surgical procedures is also discussed, opening up new possibilities in personalized therapy. This article provides up-to-date knowledge on the molecular mechanisms of CRC, diagnostic prospects, and directions for the development of precision therapies, serving as a valuable source of information for both clinicians involved in the treatment of CRC and patients wishing to deepen their knowledge of the disease and modern therapeutic options. Full article

Background: The COVID-19 pandemic prompted investigation into the interaction between SARS-CoV-2 infection and immune checkpoint inhibitor (ICI) therapy in lung cancer patients. Understanding this interplay is crucial for optimizing cancer immunotherapy. Methods: A retrospective analysis was conducted on lung cancer patients, characterizing changes in peripheral immune cells and plasma cytokines (including IL-10 and IL-12p70) before, during, and after SARS-CoV-2 infection. Progression-free survival (PFS) was compared between ICI-treated patients with and without COVID-19. Cytokine dynamics were further analyzed in a non-infected cohort. Results: SARS-CoV-2 infection induced a prolonged systemic cytokine storm, with elevated IL-10 and IL-12p70 levels and reduced monocyte proportions lasting up to 10 weeks post-recovery. Despite this immune perturbation, COVID-19 did not impair long-term PFS; instead, a transient improvement in disease control was observed in infected patients. In non-infected patients, sustained or increased IL-10 and IL-12p70 levels during ICI therapy were associated with longer PFS (p < 0.05). Conclusions: SARS-CoV-2 infection transiently alters the immune landscape in lung cancer patients without compromising ICI efficacy. The sustained elevation of IL-10 and IL-12p70 may contribute to short-term clinical benefits. Monitoring cytokine dynamics could serve as a prognostic tool for predicting ICI response. Full article

Background: The optimal timing of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) remains a subject of debate, particularly in the immunotherapy era. This study compares survival outcomes between deferred CN (dCN) and upfront CN (uCN) in mRCC patients receiving modern immunotherapy regimens in the real-world setting. Methods: We retrospectively analyzed the SEER database for mRCC patients diagnosed between 2016 and 2021 who underwent dCN or uCN. The primary endpoint was overall survival (OS), while the secondary endpoints were disease-specific survival (DSS) and other-cause specific survival (OCSS). Statistical analyses included propensity score matching (PSM), Kaplan–Meier survival curves, Cox proportional hazards modeling, as well as sensitivity, subgroup, and landmark analyses. Results: A total of 1892 mRCC patients were included, with 346 patients (18.3%) undergoing dCN and 1546 patients (81.7%) receiving uCN. Patients in the uCN group were characterized with lower T stage (p < 0.001), while those in the dCN group exhibited a higher incidence of lymph node involvement (p = 0.02) and sarcomatoid dedifferentiation (p = 0.002). Following 1:2 PSM, dCN demonstrated significantly better OS and DSS, but comparable OCSS to uCN. The sensitivity and subgroup analyses suggested that dCN may substantially improve the prognosis of mRCC patients across conditions. The landmark analysis showed that the survival advantage of dCN diminished after two years of follow-up. Conclusions: dCN may be associated with improved survival outcomes compared to uCN in selected mRCC patients receiving immunotherapy, and careful patient selection for dCN or uCN is essential. Full article

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer with a poor prognosis. Negative-margin resection is presently the only potentially curative treatment option. Emerging trends with direct applicability to surgical strategy include margin thickness, lymphadenectomy, optimization of future liver remnant (FLR), minimally invasive techniques, incorporation of systemic therapy, and reconsideration of liver transplantation. This review emphasizes areas of consensus and ongoing debate. Margins ≥5–10 mm are associated with improved results, but biology generally takes precedence over prognosis. Regional lymphadenectomy enhances staging accuracy, although its therapeutic benefit remains unsettled. PVE is standard for FLR enlargement, LVD provides faster hypertrophy, and ALPPS remains reserved for highly selective cases. Minimally invasive and robotic hepatectomy share oncologic results in skilled institutions. Systemic therapies, including immunotherapy and biomarker-directed targeted therapy, are increasingly being incorporated perioperatively. Liver transplant may be of potential value in early-stage disease or on strict indications after neoadjuvant treatment. The modern surgical management of iCCA encompasses a blend of oncologic considerations, FLR optimization, minimally invasive surgery, and systemic therapy according to tumor biology. Multidisciplinary planning and participation in clinical trials are necessary to align surgical innovation with advancements in molecular and systemic treatments, ultimately leading to improved long-term outcomes. Full article

Background/Objectives: Natural products exhibit significant immunomodulatory potential but face severe efficacy loss in three-dimensional (3D) tumor models. This review comprehensively examines the penetration–activity trade-off and proposes integrated strategies for developing effective natural product-based cancer immunotherapies. Methods: We analyzed formulation strategies across three natural product categories (hydrophobic, macromolecular, stability-sensitive), evaluating penetration enhancement versus activity preservation in spheroids, organoids, and advanced 3D platforms. Results: Tumor spheroids present formidable barriers: dense extracellular matrix (33-fold increased fibronectin), pH gradients (7.4 → 6.5), and extreme cell density (6 × 10⁷ cells/cm³). While nanoparticles, liposomes, and cyclodextrins achieve 3–20-fold penetration improvements, biological activity frequently declines through conformational changes, incomplete release (10–75%), and surface modification interference. Critically, immune cells remain peripheral (30–50 μm), questioning deep penetration pursuit. Patient-derived organoids display 68% predictive accuracy, while emerging vascularized models unveil additional complexity. Food and Drug Administration (FDA) Modernization Act 2.0 enables regulatory acceptance of these advanced models. Conclusions: Effective therapeutic outcomes depend on maintaining immunomodulatory activity in peripherally-located immune cell populations rather than achieving maximum tissue penetration depth. Our five-stage evaluation framework and standardization protocols guide development. Future priorities include artificial intelligence-driven optimization, personalized formulation strategies, and integration of multi-organ platforms to bridge the critical gap between enhanced delivery and therapeutic efficacy. Full article

Cutaneous metastases from breast carcinoma represent a debilitating complication of advanced disease progression, significantly impacting patients’ quality of life. Electrochemotherapy (ECT), which combines cytotoxic drugs such as bleomycin or cisplatin with electric pulses to enhance cellular permeability, has shown promising efficacy as a local treatment for these lesions. Objectives: This literature review examines the principles of ECT, its mechanisms of action and the clinical outcomes in patients with primary breast cancer. Across clinical series, patient-level ORR typically ranges from ~70–90% and CR up to ~58% at 6–12 weeks, with lower rates in larger (>3 cm) or deeper lesions. ECT is safe, well tolerated, and potentially synergistic with other systemic therapies. However, its efficacy is influenced by factors such as lesion size, tumor receptor status, and prior radiotherapy. Optimizing patient selection, standardizing treatment protocols, and developing combination approaches with immunotherapy or targeted therapies represent key future directions to improve clinical outcomes. Full article

Hepatocellular carcinoma (HCC) management has evolved remarkably with the advent of diverse therapeutic options, particularly systemic and surgical treatments. Combination immunotherapy has redefined the treatment paradigm for advanced HCC and contributed to improved patient outcomes. However, this brings forth challenges such as immune-related adverse events that complicate decision-making. Surgical strategies have expanded with the emergence of conversion therapy and borderline resectability, offering curative potential for a broader patient population. However, robust evidence of their long-term efficacy is lacking. Therefore, decision-making biomarkers have gained prominence across treatment modalities. This review explores the current landscape of predictive, prognostic, and treatment-response biomarkers in HCC, from molecular and immune signatures to radiological and biochemical markers, highlighting their role in optimizing therapeutic strategies. By integrating recent advances in basic and translational research with clinical practice, we aim to outline a biomarker-driven framework for individualized care in HCC. Full article

Background: Breast cancer is the most common female cancer in Italy. Despite better survival rates, significant disparities in access to diagnosis, treatment, and follow-up persist across regions. We propose an integrated, multidisciplinary care model—the Breast Immunology Network (BIN)—to address these challenges. Methods: The model was developed through a two-phase expert consultation with key opinion leaders and stakeholders, aligned with national and European oncology guidelines. No new patient data were collected; this is a qualitative analysis based on expert consensus and existing literature. The proposed model integrates a Hub-and-Spoke cancer network structure with fully functioning multidisciplinary teams (MDTs), standardized care pathways (PDTA), and digital tools to ensure continuity of care. Results: Experts identified critical gaps in Italy’s breast cancer care: limited access to specialized centers, inconsistent adherence to screening programs, and delays in treatment initiation. The proposed BIN model aims to bridge these gaps by enhancing collaboration across all care levels, incorporating immunotherapy where appropriate, and defining key performance indicators (KPIs) for continuous quality evaluation. For example, quantitative targets include achieving ≥65% nationwide mammography screening adherence and ensuring ≥90% of patients are treated in certified Breast Units. Conclusions: The Breast Immunology Network offers a strategic framework to improve equity, quality, and timeliness of breast cancer care in Italy. Importantly, unlike existing Hub–Spoke or CCCN models, the BIN formalizes governance tools, harmonized eligibility criteria, and a national registry for immunotherapy. By uniting Breast Units and community services under shared governance, and by integrating innovations such as immunotherapy and telemedicine, the BIN model could significantly improve clinical outcomes and ensure more equitable care for all patients. Its implementation may serve as a reference model for other health systems seeking to optimize oncology pathways through multidisciplinary integration and advanced treatments. Full article

Background: Immune checkpoint inhibitors (ICIs) have transformed outcomes in advanced cancers; however, the value of continuing treatment after radiologic progression remains uncertain. We systematically assessed the efficacy and safety of ICI continuation beyond progression, focusing on the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Methods: PubMed/MEDLINE, Embase, and the Cochrane Library were searched from inception to 31 March 2025. Eligible reports included retrospective cohorts, prospective trials, post hoc analyses, and pooled regulatory reviews that compared outcomes after ICI continuation versus discontinuation or historical controls. Quality was appraised with the Newcastle–Ottawa Scale (observational designs) and the Cochrane Risk-of-Bias tool (randomized trials). Results: Fifty studies involving 8989 patients met the inclusion criteria: 41 retrospective cohorts; 6 post hoc analyses; 2 randomized trials (1 phase III, 1 phase II); and 1 pooled FDA review. Continuing ICIs beyond progression produced ORRs of 9.3–39% in non-small cell lung cancer (n = 5102), 14–100% in melanoma (n = 669), and 8–33% in renal cell carcinoma (n = 458). Median OS ranged from 8.9 to 18.2 months in lung cancer, 12 to 29.9 months in melanoma, and up to 34.8 months in RCC. Modest but clinically meaningful benefits were reported in colorectal, head-and-neck, gastric, liver, and urothelial tumors. Conclusions: Select patients—particularly those with melanoma, lung cancer, RCC, or gastric cancer—may derive sustained benefit from ICI therapy after radiologic progression. Decisions should incorporate tumor biology, performance status, and emerging biomarkers. Prospective, biomarker-driven trials are needed to define optimal patient selection and the duration of post-progression immunotherapy. Full article