Search Results (999)

The role of immunotherapy in oncohematology is well established. Monoclonal antibodies have undergone substantial development in recent years, targeting a wide range of molecules (including surface antigens, immune checkpoints, and cytokines) and have demonstrated clinical utility across various hematologic malignancies, including leukemias, lymphomas, and myelomas. The emergence of advanced therapy medicinal products (ATMPs), particularly chimeric antigen receptor (CAR) T cells, has provided an additional and promising therapeutic option. This rapidly evolving field continues to expand therapeutic possibilities. The objective of this literature review is to summarize novel immunotherapeutic strategies in oncohematology, including monoclonal antibody- and CAR T-cell-based approaches, and to review the key findings from recent clinical trials. Full article

Objective: To evaluate whether human adipose-derived mesenchymal stem cells (ADSCs) protect against ᴅ-galactose (ᴅ-gal)-induced aging-like testicular injury and to investigate the involvement of the Keap1/Nrf2 pathway and NLRP3-associated pyroptosis. Methods: A mouse model of aging-like testicular injury was established by subcutaneous administration of ᴅ-gal for 8 weeks, followed by tail vein injection of ADSCs. Testicular morphology, blood–testis barrier (BTB) integrity, and senescence-associated markers (p16, p21) were assessed. In vitro, TM4 Sertoli cells were used to establish a senescence model and Tranwell co-cultured with ADSCs. Oxidative stress, inflammatory responses, and pyroptosis-related markers were evaluated using biochemical assays, immunofluorescence, Western blotting, and RT-qPCR. The involvement of the Keap1/Nrf2-NLRP3 axis was further examined using pharmacological inhibitors. Results: ADSC treatment significantly alleviated ᴅ-gal-induced testicular atrophy and histopathological injury, accompanied by reduced expression of the senescence markers p16 and p21 and partial restoration of BTB-related structures. ADSCs also attenuated oxidative stress, as evidenced by decreased ROS and MDA levels, increased SOD activity, and enhanced expression of Nrf2 and its downstream antioxidant targets, including HO-1 and NQO1. In parallel, ADSC administration suppressed NLRP3 activation, reduced caspase-1 cleavage, and lowered the expression of pro-inflammatory cytokines. In TM4 cells, inhibition of Nrf2 weakened the protective effects of ADSCs and was accompanied by reactivation of NLRP3-associated signaling, whereas inhibition of NLRP3 attenuated senescence- and inflammation-related changes without restoring Nrf2 activity. Conclusions: ADSCs alleviate ᴅ-gal-induced aging-like testicular injury, at least in part, by restoring redox balance, preserving BTB-associated structure, and suppressing NLRP3-associated pyroptosis through the Keap1/Nrf2 pathway. These findings suggest that ADSC-based therapy may represent a promising strategy for age-related male reproductive dysfunction, while further studies using genetic models and functional fertility endpoints are needed to confirm causality and translational relevance. Full article

Background: Sports-related musculoskeletal injuries, including tendon, ligament, muscle, and cartilage damage, often heal slowly and incompletely. Current treatments may not fully restore tissue function, necessitating regenerative therapies. Objective: This study was conducted to review the therapeutic potential of stem cell-derived extracellular vesicles (EVs) and conditioned medium (CM) as cell-free approaches to treating musculoskeletal injuries in sports medicine. Methods: A narrative review of preclinical and early clinical studies investigating the biological mechanisms and regenerative effects of mesenchymal stem/stromal cell (MSC)-derived EVs and CMs published between 2019 and 2026 was performed by searching Scopus, PubMed, Web of Science, and Google scholar. Results: EVs and CMs contain bioactive molecules, including microRNAs, cytokines, and growth factors, that modulate inflammation, promote tissue repair, enhance angiogenesis, and support extracellular matrix remodeling. Preclinical studies demonstrate improved healing of tendons, ligaments, muscles, and cartilage, while early clinical evidence suggests favorable safety and promising therapeutic outcomes. However, the variety of MSC sources, EV separation methods, characterization procedures, and treatment protocols present major challenges in determining the reliability and therapeutic efficacy of these therapies. Notably, the number of clinical studies on EV and CMs is still limited, and most of the available studies are in vitro studies. Conclusions: MSC-derived EVs and CMs represent promising cell-free regenerative therapies for sports-related musculoskeletal injuries. The available evidence, which demonstrates their ability to enhance healing while avoiding the challenges associated with cell-based therapies, highlights their translational potential. However, most of the studies that are now available are preclinical or early-stage clinical studies, and there is still a limited number of clinical trials. Further well-designed clinical studies are needed to establish standardized protocols and confirm long-term safety. Full article

Vitiligo is an autoimmune depigmenting disorder characterized by marked heterogeneity in therapeutic response, both between patients and among lesions within the same individual. While current therapies primarily target interferon-γ (IFN-γ)-driven inflammation, clinical outcomes remain variable and frequently incomplete, suggesting that additional lesion-specific biological factors contribute to repigmentation potential. In this narrative review, we propose the concept of repigmentation competence to describe the capacity of an individual lesion to achieve clinically meaningful repigmentation under therapy. We hypothesize that this competence emerges from the interaction of four interconnected biological axes: (i) cytokine network and immune memory, (ii) local immune regulation, (iii) regenerative capacity, and (iv) microenvironmental permissiveness. A targeted search of PubMed/MEDLINE and ClinicalTrials.gov up to March 2026 was conducted to identify translational studies, mechanistic models, and clinical trials relevant to these pathways. Evidence was synthesized thematically with emphasis on cytokine-mediated mechanisms and their interaction with regenerative and tissue-context processes. The IFN-γ/CXCL9/CXCL10 axis and tissue-resident memory T cells (TRM) represent the most clinically validated drivers of disease persistence, as demonstrated by the therapeutic efficacy of JAK inhibitors, although immune suppression alone often fails to achieve complete or durable repigmentation. In contrast, regulatory pathways involving PD-1/PD-L1 signaling, regulatory T cells (Tregs), IL-10, TGF-β, and IL-2–based strategies remain biologically compelling but only partially translated into effective therapies. Regenerative capacity has also emerged as an important determinant of treatment response, with growing evidence supporting the role of melanocyte stem cell niches, follicular regeneration, and Wnt/β-catenin signaling. Accordingly, regenerative approaches such as non-cultured epidermal cell suspension (NCES) are increasingly being integrated into combination therapeutic strategies. The lesional microenvironment remains the least therapeutically developed axis despite growing experimental evidence supporting its importance in melanocyte survival and migration. Collectively, these observations suggest that the variable efficacy of current therapies may reflect different combinations of lesion-specific biological constraints. The emerging benefit of combination strategies may therefore derive not simply from additive effects, but from the simultaneous engagement of multiple axes involved in repigmentation competence. Our review supports a shift from a predominantly drug-centered model toward a lesion-oriented framework integrating immune, regenerative, regulatory, and microenvironmental determinants of response. Full article

Background/Objectives: Persistent inflammation and impaired tissue regeneration delay mucosal and cutaneous wound healing. Potato (Solanum tuberosum L.) preparations contain bioactive metabolites with anti-inflammatory and regenerative potential, yet their wound-healing mechanisms have not been systematically mapped. This scoping review aimed to map potato-derived bioactive metabolites and their roles in modulating inflammation and promoting tissue regeneration during wound healing. Methods: A scoping review was conducted in accordance with the PRISMA-ScR guidelines. Articles published between 2015 and 2025 were retrieved from the Scopus, PubMed, EBSCO, and ScienceDirect databases combined with hand searching. Eligible studies included in vivo animal models; mechanistically relevant in vitro studies; and limited clinical or human skin safety studies investigating potato-derived extracts, fractions, or defined preparation effects in wound, ulcer, and burn healing. Results: Among the 583 records identified, only 15 met the inclusion criteria. These studies reported five major bioactive metabolite classes—flavonoids/anthocyanins, polyphenols, alkaloids, polysaccharides, and peptides—together with potato-derived exosomal vesicles as an extracellular vesicle/delivery system (not a metabolite class). Potato-derived preparations have been associated with accelerated wound closure, enhanced fibroblast proliferation, collagen deposition, and the attenuation of inflammatory mediators. Molecular evidence, which was included in only six studies, supported the modulation of NF-κB, STAT1/3, COX-2, iNOS, cytokines, and MMP-9. In addition, five priority gaps were identified: lack of standardization, fragmented biomarker profiling, limited compound-specific validation, scarce clinical translation, and absence of omics-based and complex wound models. Conclusions: Potato-derived bioactive metabolites show multi-target preclinical associations with wound healing and warrant further development as potential adjunctive therapies for mucosal and cutaneous wounds after standardization and clinical validation. Full article

Lung cancer remains the leading cause of cancer-related mortality worldwide, and durable benefit from immune checkpoint inhibitors is limited by immune exclusion, microenvironmental immunosuppression, and toxicity. This narrative translational review evaluates whether endobronchial intratumoral delivery of immuno- and gene-based therapies can transform bronchoscopic access into a therapeutic platform linking local tumour intervention with systemic antitumour immunity. We synthesise evidence on endobronchial ultrasound, electromagnetic navigation bronchoscopy, and robotic-assisted bronchoscopy, together with local checkpoint blockade, cytokine and mRNA-lipid nanoparticle constructs, oncolytic virotherapy, dendritic-cell approaches, viral and non-viral gene transfer, and enzyme- or metabolite-based strategies. Current clinical evidence remains preliminary, consisting mainly of Phase I trials, small prospective cohorts, and case-based signals, with feasibility and safety observations but no completed randomised trial demonstrating efficacy against standard-of-care systemic therapy. The most plausible candidates are patients with advanced or recurrent NSCLC, bronchoscopically accessible lesions, inadequate response to systemic immunotherapy, and immune-excluded or locally immunosuppressed tumours. Biomarkers such as PD-L1, tumour mutational burden, CD8+ infiltration, tertiary lymphoid structures, radiomics, and circulating tumour DNA require validation. This review integrates delivery technology, immune mechanisms, statistical evidence appraisal, biomarker limitations, AI-guided planning, and global feasibility. Full article

Immune-mediated temporomandibular joint disorders involve cytokine-driven inflammation and may represent a target for biologic therapy. This paper summarizes the evidence on intra-articular monoclonal antibody administration in temporomandibular joint disorders. PubMed, Europe PMC, and BASE were searched from inception to 7 April 2026 for clinical and preclinical studies evaluating intra-articular monoclonal antibodies in the temporomandibular joint. Four studies were identified: two retrospective clinical studies, one case report, and one preclinical study. All four studies investigated local TNF-α blockade: the three clinical studies used infliximab, whereas the preclinical study used an anti-rabbit TNF-α monoclonal antibody. Symptomatic benefit was confined to one adult case and anti-inflammatory effects to the preclinical study, whereas pediatric MRI abnormalities persisted or worsened, providing no evidence of structural efficacy. The evidence remains limited, heterogeneous, and exploratory. Intra-articular monoclonal antibody therapy is biologically plausible, but its clinical efficacy and safety require further investigation. Full article

Background: Metronomic chemotherapy (MCT), understood as continuous, low-dose cytotoxic administration without prolonged drug-free intervals, has become an established strategy in several solid tumors, acting primarily through antiangiogenic, immunomodulatory, and direct cytostatic mechanisms rather than replication-dependent cytotoxicity. Despite an expanding evidence base, including positive randomized trials, validated predictive biomarkers of response remain unavailable. Methods: We searched PubMed/MEDLINE, Embase, and ClinicalTrials.gov (January 2000 to July 2026) for phase II/III randomized trials, prospective cohorts, and selected retrospective analyses of MCT in breast cancer, head and neck squamous cell carcinoma, NSCLC, and mCRC, and extracted biomarker data from embedded translational substudies of eligible trials. Results: In breast cancer, phase III SYSUCC-001 (adjuvant metronomic capecitabine, improved DFS in TNBC) and MECCA (metronomic capecitabine plus aromatase inhibitor in HR+/HER2− disease) provide the strongest evidence, supported by randomized phase II data for the VEX regimen (METEORA-II) and MCT-anti-PD-1 combinations. TEMPO LUNG established metronomic vinorelbine as effective in platinum-unfit NSCLC, while CAIRO3 confirmed metronomic capecitabine–bevacizumab as an effective mCRC maintenance therapy. Most recently, the phase III TMC-I trial extended positive randomized evidence to head and neck cancer. Candidate biomarkers span angiogenic, immune, tumor proliferative, molecular, pharmacodynamic cytokine, on-treatment clinical (adverse-event-based), and gut–microbiome domains, with FOXC1, circulating endothelial cell kinetics, VEGF pathway markers, and regulatory T-cell dynamics among the most promising; however, none has been prospectively validated in a dedicated confirmatory trial. Conclusions: MCT has moved from empirical use to an evidence-based strategy across multiple tumor types, but the lack of validated predictive biomarkers limits informed patient selection. Future trials should incorporate biomarker-driven designs, particularly FOXC1, endothelial cell kinetics, and immune profiling as co-primary objectives. Defining an MCT-sensitive biological phenotype remains the key translational challenge for the field. Full article

Inflammatory bowel disease (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic inflammatory disorder characterized by dysregulated host–microbiota interactions, epithelial barrier dysfunction, and aberrant immune activation. Despite advances in biologic and small-molecule therapies, a substantial proportion of patients exhibit incomplete response, loss of response, or treatment-related adverse effects, underscoring the need for novel adjunctive therapeutic approaches. The vagus nerve exerts a pivotal effects on immune homeostasis through the cholinergic anti-inflammatory pathway, thereby integrating peripheral immune sensing with central autonomic regulation. Within the context of IBD, a diminution in vagal tone has been observed to correlate with persistent mucosal inflammation and immune dysregulation. Transcutaneous auricular vagus nerve stimulation (ta-VNS) is a non-invasive neuromodulation technique that may activate vagal circuits and modulate neuroimmune signaling without surgical intervention. This review endeavors to critically evaluate the potential efficacy of ta-VNS in the context of IBD, with particular emphasis on its discernible effects on immune, epithelial barrier, microbiota-related, and autonomic biomarkers. Emerging evidence, stemming from preliminary investigations, suggests that ta-VNS may exert an influence on inflammatory cytokine profiles, epithelial tight junction integrity, gut microbial composition, and systemic autonomic balance, warranting further elucidation. In addition, the review discusses differential responses between Crohn’s disease and ulcerative colitis, summarizes current preclinical and clinical evidence, and highlights biomarker-based strategies for evaluating therapeutic response in future randomized controlled trials. Although current evidence remains preliminary and stimulation parameters are not yet standardized, ta-VNS represents a promising adjunctive neuroimmune modulation strategy in IBD. Full article

Background/Objectives: Cutaneous adverse events (cAEs) are among the most common toxicities associated with modern anticancer therapies and can significantly affect quality of life, treatment adherence, and therapeutic outcomes. This narrative review aims to provide an updated overview of the mechanisms, clinical manifestations, prognostic implications, and management strategies of cancer therapy-related cutaneous toxicities, with a particular focus on precision oncodermatology. Methods: A narrative review of the recent literature was performed, integrating evidence from clinical studies, meta-analyses, pharmacovigilance investigations, consensus guidelines, and translational research. The review examines cutaneous toxicities associated with immune checkpoint inhibitors, targeted therapies, antibody–drug conjugates, and other emerging anticancer treatments. Results: Four major axes were identified: immune disinhibition, epithelial signaling inhibition, cytotoxic epithelial injury, and cytokine-driven immune activation. Cutaneous immune-related adverse events (cirAEs) emerged as potential biomarkers of treatment efficacy, particularly vitiligo, lichenoid, and psoriasiform eruptions. Increasing evidence supports the use of steroid-sparing biologic therapies, including dupilumab, omalizumab, anti-IL-17 agents, and Janus kinase inhibitors, although prospective validation remains limited. Recent advances in immunologic endotyping have identified distinct inflammatory pathways that may enable personalized therapeutic approaches. Antibody–drug conjugates represent an expanding source of unique dermatologic toxicities requiring dedicated management strategies. Emerging biomarkers, including cytokine signatures and microRNAs, may further refine risk stratification and treatment selection. Conclusions: The management of cancer therapy-related cutaneous toxicities is evolving toward a precision medicine model integrating clinical phenotype, immunologic endotype, and biomarker profiling. Early multidisciplinary intervention and mechanism-based therapeutic strategies may improve patient outcomes while preserving anticancer efficacy. Prospective studies are needed to validate biomarker-guided and steroid-sparing approaches in oncodermatology. Full article

Crohn’s disease (CD) is a chronic inflammatory bowel disease with a rising incidence and prevalence worldwide. It is associated with Mycobacterium avium subspecies paratuberculosis (MAP). Current CD treatment strategies are based on anti-inflammatory therapies, including anti-TNF-α drugs. These treatment options provide short-term benefits and are associated with numerous side effects in CD patients. Manuka honey is distinguished from other honey by its high content of methylglyoxal (MGO). MGO, a reactive metabolite, is also generated endogenously in macrophages during infection through glycolysis; however, the amount is insufficient to neutralize the ongoing infection and subsequent tissue damage. This study examined whether exogenous, low-dose MGO can modulate MAP-driven inflammatory and glycolysis- and lactate-associated markers in infected macrophages. THP-1 macrophages were infected with the CD-associated MAP strain and then treated with MGO doses at defined time intervals. We measured markers of M1-/M2-like phenotype polarization, monocarboxylate transporters, lactate export, antioxidant responses, cytokines, and selected glycolysis- and lactate-associated markers at both the mRNA and protein levels. MGO reduced M1 signaling markers CXCL10 (p < 0.05), TNF-α (p < 0.0001), IL-1β (p < 0.01), and IL-6 (p < 0.0001). Simultaneously, MGO promoted M2 shift, elevating CD206 by 1.20-fold and IL-10 by 7-fold. Low-dose MGO administration was associated with increases in Nrf-2 (1.4-fold), HO-1 (1.4-fold), and IL-1Ra (1.5-fold), while the pro-inflammatory cytokines decreased. Metabolically, MGO downregulated MCT4 (p < 0.01) and reduced lactate export by 30%. These changes were coupled with higher PHD2 (1.4-fold) and decreases in GLUT1 (0.9-fold), PKD1 (0.8-fold), and IL-1β, consistent with attenuated glycolysis- and lactate-associated inflammatory signaling. These results suggest that hormetic concentration of MGO mitigates MAP-induced inflammatory activation while altering glycolysis- and lactate-related signaling markers in infected macrophages. Most importantly, we unraveled the predicted molecular mechanism by which MGO suppresses inflammation and modulates oxidative damage. Full article

Proteins and associated post-translational modifications are receiving deserved attention in the search for immune therapies to combat a long list of diseases, including a number of fatal forms of cancer. Such attention has been fueled by a number of clinical results generated by numerous clinical trials, together with datasets generated by academic research. The title of this review is based on a couple of considerations: most, if not all, researched immune checkpoints are proteins, each of which can experience one or more post-translational modifications (PTMs). It is also known that among the main functions of post-translational modifications is their direct impact on protein localization. Given that most activities of known checkpoints are performed on the surface of the host cells, post-translational modifications are bound to influence the role of these proteins, both as drivers of various diseases and as therapeutic targets. The second consideration concerns another class of proteins, which is responsible for a severe toxic reaction in the immune system following treatment with immune cell inhibitors, a reaction known as cytokine release syndrome (CRS). Cytokines are low-molecular-weight proteins, among which the key members are interleukin-1 (IL-1), interleukin-6 (IL-6), and interferon γ (IFN-γ). A number of clinical trials have shown that the symptoms of CRS toxicities are frequently accompanied by elevated levels of cytokines, including IL-6 and IFN-γ. The recent literature suggests that we still need to know more about the biology of these proteins and the type of modifications that these key members of cytokines can experience. Such additional knowledge may contribute to more effective and safer immune cell therapy. The contribution of mass-spectrometry-based proteomics to the investigation of PTMs associated with immune checkpoints and cytokines is discussed. Full article

Osteoarthritis (OA) is a significant clinical problem that places a substantial burden on both patients and the healthcare system. Characterized by progressive cartilage degeneration, synovial inflammation, and subchondral bone remodeling, OA is a rapidly growing and increasingly studied disease affecting millions around the world. Growing evidence has expanded on the traditional view of OA as a mechanical “wear-and-tear” disease, highlighting that disease progression is driven not only by mechanical stress but also by chronic dysregulation of the osteoimmune environment. Activation of innate and adaptive immune pathways, macrophage M1 polarization, and dysregulated cytokine signaling all contribute to progressive joint degeneration. While current therapeutics often focus on managing symptoms or restoring joint mechanics, interventions often overlook the role of osteoimmunology in disease progression. This review summarizes the biological and bioengineering strategies emerging to address OA. These platforms include bioceramics, metal-based scaffolds, hydrogels, nanoparticles, and microsphere systems. Furthermore, small molecules, cell-based therapies, and gene-modified systems have also been shown to modulate the inflammatory microenvironment, enhance regulatory immune responses, and restore cartilage homeostasis. Together, these approaches represent the evolving research landscape, shifting away from just symptom alleviation and towards targeted disease-modifying therapies, including osteoimmunomodulation. However, significant barriers to clinical translation remain, such as limited large animal studies and species immune system differences, which need to be addressed for the development of clinically applicable interventions. 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

Acute myeloid leukemia (AML) develops within a bone marrow environment that influences leukemic stem cell behavior, residual disease, and response to therapy. This review examines evidence that the marrow microenvironment is not only a site of leukemic growth, but can actively shape AML initiation, maintenance, and treatment resistance. Clinical observations such as donor cell leukemia after allogeneic transplantation, together with experimental models in which stromal or osteolineage abnormalities induce myeloid disease, suggest that altered niches may contribute to leukemogenesis in selected settings. In established AML, vascular and endosteal compartments provide adhesive, chemokine, inflammatory, and metabolic signals that promote leukemic-cell retention, quiescence, survival, and chemotherapy tolerance. AML cells also remodel the surrounding marrow, suppressing normal hematopoiesis and generating stromal, endothelial, osteoblastic, adipocytic, and immune-cell programs that favor leukemic persistence. These interactions are especially relevant to drug resistance, including resistance to venetoclax-based therapy, where cytokine-mediated changes in apoptotic dependence, fatty-acid metabolism, mitochondrial adaptation, and stromal support may all contribute. Several therapeutic approaches have attempted to disrupt niche-mediated protection, including targeting CXCL12/CXCR4 signaling, adhesion pathways, inflammatory circuits, Hedgehog signaling, and metabolic dependencies. Although early-phase studies have shown activity in some AML subsets, randomized evidence remains limited and results have been inconsistent. We discuss how a better understanding of microenvironmental biology may help define when niche-directed therapy is most likely to complement conventional and molecularly targeted AML treatment. Full article