Melanoma is a type of skin cancer with an increasing incidence rate worldwide and a high mortality rate. In addition to known risk factors, such as UV exposure and genetic predisposition, researchers are paying more attention to the role of diet, micronutrients, and vitamins in preventing melanoma. This review discusses the effects of selected vitamins (D, A, C, and E), trace elements, and bioactive compounds (polyphenols and omega-3 fatty acids) on biological processes related to melanoma development. The review considered both antioxidant and immunomodulatory effects, as well as effects on DNA repair and photoprotection. The significance of polymorphisms of genes encoding receptors and enzymes that metabolize the compounds studied was also analyzed. The results suggest that maintaining adequate levels of these substances may promote melanoma prevention, particularly among individuals at risk. However, caution in the use of supplementation is necessary due to the possible biphasic effects of some micronutrients. Further clinical trials are needed to develop effective, safe prevention strategies based on micronutrients and vitamins.

Metastatic uveal melanoma (MUM) remains largely refractory to immune-checkpoint inhibition, so recent research has turned to bispecific T-cell engagers (BTCEs), adoptive-cell therapies (ACTs), and oncolytic viruses (OVs). To summarize the available clinical evidence, we performed a structured literature search across PubMed, Scopus, and Europe PMC for primary studies published between 1 January 2010 and 31 May 2025 that enrolled at least three adults with MUM, treated with one of these modalities, and that reported efficacy or grade-3+ safety outcomes; two reviewers independently performed screening, data extraction, and risk-of-bias assessment, and because of notable heterogeneity, we synthesized the findings narratively. Twenty-two studies met the criteria—thirteen phase I–III trials, eight observational cohorts, and one case series—covering fifteen BTCE cohorts, four ACT cohorts, and three OV cohorts. Tebentafusp, the dominant BTCE evaluated in roughly 1150 HLA-A*02:01-positive patients, extended median overall survival from 16.0 to 21.7 months (hazard ratio 0.51, with three-year follow-up HR 0.68) in its pivotal phase-III trial despite objective response rates of only 5–12%, with early skin rash and week-12 circulating-tumor-DNA clearance emerging as consistent markers of benefit. Tumor-infiltrating lymphocyte therapy, administered to about thirty patients, produced objective responses in 11–35% and occasional durable complete remissions, although median progression-free survival remained 2–6 months and severe cytopenias were universal. Three early-phase OV studies, totaling twenty-nine patients, yielded no radiographic responses but showed tumor-specific T-cell expansion and transient disease stabilization. Safety profiles reflected the mechanism of action: tebentafusp most often caused rash, pyrexia, and usually manageable cytokine-release syndrome with grade-3+ events in 40–70% yet discontinuation in roughly 2%; TIL therapy toxicity was driven by lymphodepleting chemotherapy and high-dose interleukin-2 with one treatment-related death; and OVs were generally well tolerated with no more than 20% grade-3 events.

TLS are ectopic, non-encapsulated aggregates of immune cells that develop de novo in non-lymphoid tissues in response to persistent antigenic stimulation, and have emerged as clinically relevant features of many solid tumours. However, conventional TLS assessment based on presence/absence, density, or simplified maturation scales does not adequately explain why TLS are associated with favourable, neutral, or even adverse clinical outcomes across tumour types and treatment settings. In this review, we synthesize current biological, spatial, and clinical evidence and argue that TLS should be interpreted not as static histologic findings, but as functional immune niches shaped by three interacting axes: structural maturity, spatial localization, and functional immune context. We discuss how mature germinal centre-positive TLS often reflect coordinated B-cell–T-cell cooperation and sustained antigen-driven antitumour immunity, whereas partially organised or suppressive TLS may display transitional or immunoregulatory properties. On this basis, we propose a pragmatic, pathology-oriented conceptual framework that groups TLS into three simplified functional states: TLS-A, representing mature effector TLS with germinal centre activity; TLS-B, representing organised but incompletely matured or functionally intermediate TLS; and TLS-C, representing TLS dominated by regulatory or suppressive immune programs. We further place these states within recurrent tumour microenvironment archetypes and outline the rationale for a “functional TLS score” integrating histopathologic and molecular readouts. Rather than introducing a definitive biological taxonomy, this framework is intended as a translational model for harmonising TLS interpretation, refining biomarker development, and supporting future studies on prognosis, immunotherapy response, and standardised pathology reporting in solid tumours.

TLSs are ectopic, non-encapsulated aggregates of immune cells that develop de novo in non-lymphoid tissues in response to persistent antigenic stimulation and have emerged as clinically relevant features of many solid tumours. However, conventional TLS assessment based on presence/absence, density, or simplified maturation scales does not adequately explain why TLSs are associated with favourable, neutral, or even adverse clinical outcomes across tumour types and treatment settings. In this review, we synthesise the current biological, spatial, and clinical evidence and argue that TLSs should be interpreted not as static histologic findings but as functional immune niches shaped by three interacting axes: structural maturity, spatial localisation, and the functional immune context. We discuss how mature germinal centre-positive TLSs often reflect coordinated B-cell–T-cell cooperation and sustained antigen-driven anti-tumour immunity, whereas partially organised or suppressive TLSs may display transitional or immunoregulatory properties. On this basis, we propose a pragmatic, pathology-oriented conceptual framework that groups TLSs into three simplified functional states: TLS-A, representing mature effector TLSs with germinal centre activity; TLS-B, representing organised but incompletely matured or functionally intermediate TLSs; and TLS-C, representing TLSs dominated by regulatory or suppressive immune programs. We further place these states within recurrent tumour microenvironment archetypes and outline the rationale for a “proposed functional TLS score” integrating histopathologic and molecular readouts. Rather than introducing a definitive biological taxonomy, this framework is intended as a translational model for harmonising TLS interpretation, refining biomarker development, and supporting future studies on prognosis, immunotherapy response, and standardised pathology reporting in solid tumours. Because this framework is derived from a narrative synthesis of published evidence rather than from formal validation, it should be regarded as hypothesis-generating and requires prospective, tumour-specific validation before clinical implementation.

Chronic liver disease is characterised not only by persistent injury and fibrosis, but also by a progressive shift from adaptive hepatocyte-driven repair toward maladaptive tissue remodelling. Although liver regeneration is often discussed as a compensatory response, chronic injury may render this process structurally and functionally dysregulated, thereby promoting architectural distortion, fibrosis progression, and a microenvironment permissive for hepatocarcinogenesis. In this narrative review, we propose that this transition can be interpreted through three interconnected, histopathology-anchored endpoints: ductular reaction, extracellular matrix remodelling, and parenchymal extinction. We discuss ductular reaction as a progenitor niche phenotype that emerges when effective hepatocyte regeneration is impaired and becomes increasingly linked to portal inflammation, fibrogenic signalling, and altered cell–matrix interactions. We then examine extracellular matrix remodelling as a central tissue-level process involving activated stellate cells, portal fibroblasts, macrophages, cholangiocytes, and dysfunctional endothelial cells, resulting in collagen accumulation, increased stiffness, fibrous septa formation, and progressive reorganization of the hepatic microenvironment. Finally, we address parenchymal extinction as a morphological endpoint of often-irreversible or incompletely reversible hepatocyte loss accompanied by microvascular injury, ischaemia, and fibrotic replacement, contributing directly to architectural collapse and disease advancement. Rather than representing isolated phenomena, these three processes form a biologically integrated remodelling axis that links failed regeneration with fibrosis progression and malignant transformation. By framing chronic liver disease through these assessable histologic endpoints, this review aims to provide a more coherent pathology-oriented model of progression and to highlight mechanisms that may improve tissue-based risk stratification and future translational research.

The introduction of immune checkpoint inhibitors (ICIs) into the treatment of melanoma has significantly reduced mortality over the past decade. However, therapeutic benefit is not observed in all patients, and treatment may be associated with severe adverse events. Therefore, identifying patients who are most likely to benefit from immunotherapy remains of critical importance. Currently used biomarkers, such as programmed death-ligand 1 (PD-L1) expression and manual assessment of tumour-infiltrating lymphocytes (TILs), have limited predictive value. This narrative review provides a critical appraisal of studies employing digital pathology tools, multiplex and spatial techniques (including multiplex immunofluorescence, imaging mass cytometry, and digital spatial profiling), as well as machine learning algorithms for predicting response to ICIs in patients with melanoma. Available evidence suggests that the highest predictive value may be achieved by approaches integrating quantitative assessment of immune infiltration with information on its spatial distribution, functional state, and interactions within the tumour microenvironment. Particular relevance may be attributed to features associated with the “immune-inflamed”, “immune-excluded”, and “immune-desert” phenotypes, the presence of tertiary lymphoid structures, and the organisation of local immune niches. In addition, this review highlights key limitations in the interpretation of current data, including lack of methodological standardisation, data heterogeneity, and insufficient validation. Directions for future research necessary for the implementation of these approaches into routine clinical practice are also discussed.