Search Results (577)

Dendritic cells (DCs) are a heterogeneous population known for antigen presentation and immune modulation, playing a key role in priming a T cell response against pathogens and tumor cells. Despite their putative therapeutic value, their scarcity in peripheral blood limited their direct use in therapeutic applications until recently. The discovery that DCs can be generated from circulating monocytes ex vivo, however, gave a boost of extensive research in the use of DCs in clinical applications. Still, despite the numerous clinical trials, the introduction of DCs in the everyday clinical oncology practice is delayed. In this narrative review, we provide an updated summary of the field covering the theoretical and practical aspects of the concept of the use of DCs in adoptive cellular immunotherapy and the completed or ongoing clinical trials for the use of these species in clinical oncology practice. To better understand the current developments of the field, we included those clinical trial reports that published evaluable data to date. Based on our literature survey, DC-based adoptive cellular therapy is a safe therapeutic intervention with valuable clinical potential. Its widespread implementation, however, is likely delayed due to a number of factors that make meaningful evaluation of clinical trial results complicated. These include the great variety of preclinical trial concepts, difficult and heterogenous patient cohorts, and the diversity of intervention techniques applied. Since these factors might hinder the routine implementation of DC-based applications in the more widespread forms of immunotherapy, one of the urgent short-term future directions seems to be the standardization of the DC-based methodologies. Full article

The PICO framework determines the scope of the Joint Clinical Assessment (JCA) under the EU HTA Regulation (EU HTAR), with PICO consolidation being a critical final step of the scoping process. Due to limited clarity on how consolidation works in practice, Health Technology Developers (HTDs) may simulate PICO scoping as a strategic tool to guide the development of robust JCA submissions. A review of 14 publications, representing 35 individual PICO exercises across 20 indications (74% in oncology), showed an average of 7 countries participating per exercise and 8 consolidated PICOs per analysis. A separate PICO scoping simulation focused on a first-line immuno-oncology treatment for metastatic non-small cell lung cancer (mNSCLC) generated 67 PICOs, reflecting the anticipated perspectives of 25 countries, largely driven by biomarker and histology-based sub-populations. The limited number of published examples and country participation restricts the ability to draw clear conclusions or confidently predict the output of PICO scoping in a real life JCA processes. The simulation also raised questions about whether all sub-populations should be included or consolidated further. Overall, there is a need for greater clarity in the JCA PICO scoping process, in particular the consolidation step, to facilitate high-quality evidence generation and support the EU HTAR to meet its goals of efficiency, transparency, and equity in health technology evaluation across Europe, along with more consistent patient access. Full article

Background/Objectives: Boron-dipyrromethene (BODIPY) derivatives are a superior class of fluorophores prized for their exceptional photostability and tunable photophysical properties. While ideal for imaging, their translation to photodynamic therapy (PDT) has been hampered by excitation in the visible range, leading to poor tissue penetration. To overcome this, intense research has focused on developing near-infrared (NIR)-absorbing BODIPY photosensitizers (PS). This review aims to systematically summarize the hierarchical design strategies, from molecular engineering to advanced nanoplatform construction, that underpin the recent progress of NIR-BODIPY PS in therapeutic applications. Methods: We conducted a comprehensive literature review using PubMed, Scopus, and Web of Science databases. The search focused on keywords such as “BODIPY”, “aza-BODIPY”, “near-infrared”, “photodynamic therapy”, “photothermal therapy”, “nanocarriers”, “hypoxia”, “immuno-phototherapy”, and “antibacterial.” This review analyzes key studies describing molecular design, chemical modification strategies (e.g., heavy-atom effect, π-extension), nanoplatform formulation, and therapeutic applications in vitro and in vivo. Results: Our analysis reveals a clear progression in design complexity. At the molecular level, we summarize strategies to enhance selectivity, including active targeting, designing “smart” PS responsive to the tumor microenvironment (TME) (e.g., hypoxia or low pH), and precise subcellular localization (e.g., mitochondria, lysosomes). We then detail the core chemical strategies for achieving NIR absorption and high singlet oxygen yield, including π-extension, the internal heavy-atom effect, and heavy-atom-free mechanisms (e.g., dimerization). The main body of the review categorizes the evolution of advanced theranostic nanoplatforms, including targeted systems, stimuli-responsive ‘smart’ systems, photo-immunotherapy (PIT) platforms inducing immunogenic cell death (ICD), hypoxia-overcoming systems, and synergistic chemo-phototherapy carriers. Finally, we highlight emerging applications beyond oncology, focusing on the use of NIR-BODIPY PS for antibacterial therapy and biofilm eradication. Conclusions: NIR-BODIPY photosensitizers are a highly versatile and powerful class of theranostic agents. The field is rapidly moving from simple molecules to sophisticated, multifunctional nanoplatforms designed to overcome key clinical hurdles like hypoxia, poor selectivity, and drug resistance. While challenges in scalability and clinical translation remain, the rational design strategies and expanding applications, including in infectious diseases, confirm that NIR-BODIPY derivatives will be foundational to the next generation of precision photomedicine. Full article

Cancer immunotherapy has transformed oncology, but lasting responses are still limited due to resistance mechanisms within the tumor microenvironment. MicroRNAs (miRNAs) have emerged as critical regulators of immune checkpoint pathways, antigen presentation, T-cell activity, and macrophage polarization. By modulating both tumor-intrinsic and immune cell–intrinsic processes, miRNAs influence the efficacy of immune checkpoint inhibitors, therapeutic vaccines, and adoptive cell therapies. Additionally, circulating and exosomal miRNAs are being investigated as minimally invasive biomarkers to predict patient response and resistance to immunotherapy. Clinical trials of miRNA-based treatments, including mimics and inhibitors, have highlighted both the promise and challenges of translating these molecules into clinical use. Advances in delivery systems, RNA chemistry, and combinatorial strategies are paving the way for their integration into precision immuno-oncology. This review offers a comprehensive overview of the mechanistic, biomarker, and therapeutic roles of miRNAs in cancer immunotherapy, highlighting ongoing clinical progress and prospects. Full article

Nanomedicine has now become a transformative platform that enhances the precision and efficacy of immunotherapy approaches and allows customizations like never before when it comes to cancer, as well as autoimmune conditions. Using platforms based on nanoscale, researchers have been able to manipulate immune responses operating across spatial and temporal scales to address key limitations of conventional immunotherapy associated with working with immune response such as immune evasion, systemic toxicity, and poor pharmacokinetics. Sophisticated nanoparticles (such as stimuli-sensitive ones, exosome-mimetic vesicle nanoparticles, and nanoparticles with CRISPR) allow directed immunomodulators, antigens, and gene-editing systems to reach one or more particular immune compartments. The innovations allow reprogramming of immune cells, immune tolerance rejuvenation, and expansion of antitumor immunity without significant off-target effects. Finding applications in integrating the artificial intelligence as well as multi-omics techniques, the process leads to personalization of the nano-immunotherapies based on patient-specific immuno-signatures. The chapter discusses the mechanistic rationale, therapeutic advancement, and the translational opportunities of nanotechnology-based immunotherapies that define them as part of a foundation of future generations of clinical approaches to precision immune modulation in oncology and autoimmune diseases. Full article

Background/Objectives: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy; however, their efficacy varies among patients. Eosinophils have been reported as prognostic markers in chemotherapy-treated pancreatic cancer; however, these studies are limited mainly to single cancer types and relatively small cohorts. Therefore, we aimed to examine the relationship between eosinophil count and the effectiveness of ICIs across various cancer types. Methods: We retrospectively analyzed 138 patients treated with ICI monotherapy, ICI plus chemotherapy, or chemotherapy alone at our institution between December 2015 and September 2024. Peripheral blood parameters, including eosinophil counts and albumin levels, were collected at baseline and after two cycles of treatment. Associations between overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan–Meier analysis and Cox proportional hazards regression. Results: In the ICI monotherapy group, patients with higher baseline eosinophil counts had significantly longer OS (HR 0.26, p = 0.007) and PFS (HR 0.30, p = 0.005). No significant associations were observed between the ICI plus chemotherapy and chemotherapy-alone groups. Changes in eosinophil counts between baseline and after two cycles were not associated with outcomes in any group. Conclusions: Baseline eosinophil counts were significantly associated with survival outcomes in patients receiving ICI monotherapy and may serve as a promising predictive biomarker. Full article

Personalized cancer vaccines represent a revolutionary frontier in oncology, harnessing the unique genetic and molecular profile of individual tumors to elicit targeted immune responses. This review provides a comprehensive overview of the current landscape and future perspectives of neoantigen-based personalized cancer vaccines, encompassing peptide, mRNA, DNA, autologous dendritic cell, and viral or bacterial vector platforms. We further discuss the integration of immune adjuvants, delivery systems, and combinational strategies, particularly with immune checkpoint inhibitions, to overcome tumor-induced immune exhaustion and improve therapeutic efficacy. Despite significant clinical progress over the past decade in this space, major challenges remain in immunogenic neoantigens prediction, streamlining individualized vaccine manufacturing, and optimization of combinational regimens to maximize durable antitumor responses. By reviewing recent preclinical and clinical studies on neoantigen-based cancer vaccines, this review highlights key advances, identifies persistent translational bottlenecks, and underscores the need for biomarker-guided mechanistically informed trials to fully unleash the clinical potential of neoantigen-based personalized cancer vaccines in the era of precision immuno-oncology. Full article

Background: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by providing durable survival gains, but understanding their effects on patient health-related quality of life (HRQL) is critical. Methods: We performed a narrative review of cross-sectional surveys, early-phase trials, and large-scale phase II and III randomized controlled clinical trials assessing FDA-approved ICIs, including programmed cell death protein 1 (PD-1) inhibitors, programmed death ligand 1 (PD-L1) inhibitors, and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) inhibitors, with emphasis on patient-reported HRQL. Validated HRQL instruments were summarized, and for pivotal trials, the positioning of HRQL outcomes as primary, secondary, or exploratory endpoints was taken from original protocols or primary manuscripts. Results: ICIs generally preserved or improved HRQL in patients with various malignancies compared with chemotherapy, targeted therapies, or observation. PD-1/PD-L1 inhibitors maintained global health and function and delayed symptom progression in patients with lung cancer, melanoma, and renal cell carcinoma. Regimens combining CTLA-4 blockade and PD-1/PD-L1 inhibition (e.g., nivolumab + ipilimumab, durvalumab + tremelimumab) are associated with HRQL outcomes similar or superior to those of targeted therapies. Overall, most immune-related adverse effects were short-term and did not diminish HRQL benefits. Conclusions: ICIs extend survival while preserving, and often enhancing, patient HRQL. These medications represent a shift in oncology, offering not just longer life but also better daily well-being. Continued long-term patient-reported outcome monitoring is essential to guide survivorship care in the immunotherapy era. Full article

Background/Objectives: This study aimed to characterize dendritic cell (DC) heterogeneity, immune associations, and prognostic relevance across three TP53-mutated tumor entities—high-grade serous ovarian cancer (HGSOC), triple-negative breast cancer, and endometrial cancer—focusing on plasmacytoid DCs (pDCs) in HGSOC. Methods: RNA-sequencing and clinical data of 603 patients from The Cancer Genome Atlas were analyzed. DC subset abundance was assessed for cDC progenitor, conventional DC type 1 (cDC1), conventional DC type 2 (cDC2), plasmacytoid DC (pDC), and mature DC by marker gene signatures. Differences in DC scores across tumors were analyzed using Kruskal–Wallis. Survival analyses were performed using Kaplan–Meier and Cox regression. Spearman’s correlation was used to determine associations between parameters. Results: HGSOC showed the lowest pDC abundance, yet high pDC scores were independently associated with shorter PFS (HR = 1.55, 95% CI: 1.05–2.27; p = 0.027), representing the only DC-subset-related prognostic signal observed across tumor types. pDCs correlated positively with neutrophils and negatively with monocytes, and pDCs, cDC2s, and cDC progenitors correlated inversely with TMB. No consistent link was found between pDC and TP53 mutation classes. However, tumors harboring specific TP53 mutations within established hotspot regions exhibited significantly lower pDC levels (p = 0.015). Conclusions: Our findings reveal distinct DC infiltration patterns and highlight the immunological vulnerability of TP53-mutated HGSOC. pDCs appear to exert a tumor-promoting, immune-evasive role, suggesting that DC function depends on their programming and tumor context. Selective targeting of DC subsets may offer novel therapeutic opportunities in TP53-mutated, low-TMB cancers. Full article

Transcription factors from the Zinc Finger Protein (ZFP) family are extensively implicated in tumorigenesis, yet the roles of many members, such as ZNF668, remain uncharacterized. This study presents a comprehensive pan-cancer analysis of ZNF668, investigating its expression profiles, genetic alterations, functional pathways, association with immune infiltration, and clinical correlations across cancer types from TCGA. Our pan-cancer analysis identifies ZNF668 as a frequently overexpressed gene with significant diagnostic and prognostic value. Its overexpression, often driven by gene amplification, is linked to fundamental cellular processes such as RNA splicing and transcriptional regulation. Critically, ZNF668 is implicated in promoting a state of adaptive immune resistance. While its expression positively correlates with the immunogenic MSI phenotype and suggests T-cell infiltration, this is likely offset by a dual immunosuppressive mechanism comprising a strong association with a cancer-associated fibroblast (CAF)-driven, T-cell-exhausted TME and a concurrent suppression of neutrophil recruitment. Furthermore, molecular docking identified Dasatinib as a potential ZNF668 inhibitor. These findings establish ZNF668 as a key regulator of CAF-mediated immune suppression, presenting it as a novel therapeutic target for restoring effective anti-tumor immunity. Full article

Radiolabeled monoclonal antibodies represent a promising approach to integrate molecular imaging with immunotherapy for cancer diagnosis and treatment. These antibodies target immune checkpoints and tumor-associated antigens, enabling non-invasive visualization of tumor dynamics through PET and SPECT imaging. Evidence from preclinical and clinical studies suggests that such imaging can provide insights into antibody distribution, immune cell infiltration, and potential treatment responses within the tumor microenvironment. By combining diagnostic and therapeutic capabilities, antibody-based theranostics offer opportunities for personalized treatment planning and understanding mechanisms of resistance. This review highlights current advances in antibody-based molecular imaging, discusses challenges in translation, and explores future directions for integrating imaging with immuno-oncology strategies to improve patient outcomes. Radiolabeled antibodies allow non-invasive assessment of tumor–immune interactions, supporting adaptive treatment planning and bridging immunotherapy with molecular imaging. Full article

Gastrointestinal cancers, including gastric, gastroesophageal junction, pancreatic, and biliary tract cancers, remain associated with poor outcomes due to late diagnosis and limited effective treatment options. Claudin-18.2 (CLDN18.2), a tight junction protein primarily found in the gastric epithelium and ectopically expressed in gastrointestinal tumors, has emerged as a promising therapeutic target across these diseases. This narrative review expands on existing discussions surrounding CLDN18.2-directed therapy in gastric and gastroesophageal cancer and provides a comprehensive, updated analysis of the rapidly evolving therapeutic landscape across multiple gastrointestinal malignancies, including pancreatic and biliary tract cancers. We summarize key developments following the approval of the monoclonal antibody zolbetuximab and critically evaluate emerging modalities, including bispecific antibodies, antibody–drug conjugates, and chimeric antigen receptor T-cell therapies, highlighting differences in mechanisms of action, efficacy, toxicity profiles, and mitigation strategies. We also discuss the clinical relevance of CLDN18.2 and PD-L1 co-expression, the rationale for pairing CLDN18.2-targeted therapy with immune checkpoint inhibitors, and early data supporting combination approaches. Additionally, we examine tumor heterogeneity, biomarker challenges, and emerging resistance mechanisms, alongside strategies to overcome them. Finally, we identify current limitations in the field, including inconsistent CLDN18.2 testing criteria, and outline prioritized future directions to optimize integration of CLDN18.2-directed therapies across gastrointestinal cancers. By looking beyond zolbetuximab and incorporating cross-platform comparison, immuno-oncology considerations, and multi-tumor context, this review provides a broad and forward-looking framework to guide clinical application and next-generation research in CLDN18.2-targeted therapy. Full article

Background: Radiomics enables the extraction of quantitative imaging biomarkers that can non-invasively capture tumor biology and treatment response. Delta-radiomics, by assessing temporal changes in radiomic features, may improve reproducibility and reveal early therapy-induced alterations. This study investigated whether delta-texture features from contrast-enhanced CT could predict progression-free survival (PFS) and overall survival (OS) in patients with metastatic colorectal cancer (mCRC) liver metastases treated with cetuximab rechallenge plus avelumab within the CAVE trial. Methods: This retrospective substudy included 42 patients enrolled in the multicenter CAVE phase II trial with evaluable liver metastases on baseline and first restaging CT. Liver lesions were manually segmented by two readers, and radiomic features were extracted according to IBSI guidelines. Delta-values were calculated as relative changes between baseline and post-treatment scans. Reproducibility (ICC > 0.70), univariate and multivariable analyses, ROC/AUC, bootstrap resampling, cross-validation, and decision curve analysis were performed to evaluate predictive performance and clinical utility. Results: Among reproducible features, delta-GLCM Homogeneity emerged as the most robust predictor. A decrease in homogeneity independently correlated with longer PFS (HR = 0.32, p = 0.003) and OS (HR = 0.41, p = 0.021). The combined clinical–radiomic model achieved good discrimination (AUC 0.94 training, 0.74 validation) and stable performance on internal validation (bootstrap C-index 0.77). Decision curve analysis indicated greater net clinical benefit compared with clinical variables alone. Conclusions: This exploratory study provides preliminary evidence that delta-GLCM Homogeneity may serve as a reproducible imaging biomarker of response and survival in mCRC patients receiving cetuximab plus avelumab rechallenge. If validated in larger, independent cohorts, delta-radiomics could enable early identification of non-responders and support personalized treatment adaptation in immuno-targeted therapy. Given the small sample size, the potential for overfitting should be considered. Future work should prioritize prospective multicenter validation with a pre-registered, locked model and explore multimodal integration (radiogenomics, circulating biomarkers, and AI-driven fusion of imaging with clinical/omic data) to strengthen translational impact. Beyond imaging advances, these findings align with broader trends in personalized oncology, including response-adaptive strategies, multimodal biomarker integration, and AI-enabled decision support. Full article

Background: We recently generated T cell receptor (TCR) transgenic (Tg) mice specific to cardiac myosin heavy chain-α (Myhc-α 334–352) on both myocarditis-resistant (C57BL/6) and susceptible (A/J) genetic backgrounds. We noted that the antigen-specific TCRs were expressed in CD4⁺ and CD8⁺ T cells in both strains, but their responses differed. While the T cells from naïve Tg C57BL/6 mice do not respond to Myhc-α 334–352, whereas those from A/J mice spontaneously respond to the antigen, suggesting their underlying molecular mechanisms might differ. Methods: To investigate the mechanisms of differences in the antigen-responsiveness between the Tg C57BL/6 and A/J mice, we performed bulk RNA sequencing on CD4⁺ and CD8⁺ T cells sorted by flow cytometry. Differentially expressed genes, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, gene set enrichment analysis (GSEA) of GO and KEGG, and transcription factor (TF) network analyses were performed to identify pathways and regulators of immune responses. Results: First, the principal component analysis of the transcriptomic profiles distinguished CD4⁺ from CD8⁺ T cells, which also differed between the two strains. Second, the differentially expressed cytokine and cytotoxicity genes revealed similar patterns between CD4⁺ and CD8⁺ T cells. Importantly, KEGG enrichment analysis revealed downregulated pathways in both CD4⁺ and CD8⁺ T cells that are associated with viral myocarditis, and various autoimmune conditions in C57BL/6 as compared to A/J mice. Similarly, the GSEA of GO revealed negative regulation of heart contraction and positive regulation of cardiac muscle hypertrophy processes were negatively enriched in CD4⁺ T cells of C57BL/6 mice. Finally, by generating the transcription factor (TF) networks, 22 TFs were found common to both CD4⁺ and CD8⁺ T cells, whereas eight TFs were unique to CD4⁺ or CD8⁺ T cells that have a role in T cell activation, tolerance, and T regulatory cells. Conclusions: Our data provide new insights into the transcriptomic profiles that may contribute to the genetic resistance mechanisms for developing cardiac autoimmunity. Full article