Pigment Cell & Melanoma Research最新文献

Cutaneous melanoma is a complex disease influenced by both environmental and genetic factors. Inherited susceptibility plays a significant role, involving a combination of high-, intermediate- and low-penetrance genes. Melanoma in children and adolescents has been speculated to have a stronger genetic component due to the early onset. This study investigates germline variants in early-onset melanoma through exome sequencing of 154 patients in Australia diagnosed with cutaneous melanoma before the age of 20. Potentially pathogenic variants in shelterin complex genes were identified in 3% of the cases, consistent with a role for telomere dysregulation in early-onset melanoma. MC1R R-alleles, associated with red hair, fair skin and increased melanoma risk, were less frequent than in adult cases (0.46 vs. 0.64). Pathogenic germline variants in pigmentation genes linked to albinism were identified in 11 individuals (7%), including three truncating variants in PMEL, reinforcing the role of pigmentation pathways in cutaneous melanoma susceptibility. Two patients carried mutations in MBD4, suggesting it may contribute to early-onset disease. The high frequency of rare variants in high- or intermediate-risk genes highlights the importance of including such genes in genetic tests, as they may have implications for future risk in the adolescent patients and their at-risk relatives.

Immune checkpoint inhibitor (ICI) therapy has been widely utilized across various cancer types, including melanoma. It has emerged as a first-line treatment option for metastatic melanoma. By targeting checkpoint proteins such as programmed cell death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4), ICI therapy activates the immune system, enhancing its ability to combat cancer cells, leading to long-term efficacy and potential cures in some patients. However, ICI therapy is not universally effective. Resistance and adverse reactions of ICI therapy occur in some patients. The identification of systematic biomarkers from blood tests may offer a rapid and efficient means to assess patient responsiveness to ICI therapy, as well as the risk of developing immune-related adverse events (irAEs), to facilitate individualized patient selection. This article provides a comprehensive literature review of systemic biomarkers used in melanoma patients receiving ICI therapy. The insights provide clinical professionals and researchers with valuable information for the investigation and management of melanoma patients, leading toward personalized medical decisions.

At the 2025 ESPCR (European Society for Pigment Cell Research) meeting in Erlangen, a workshop on "Pigment Cell Models: Sensitivity, Innovation, and the Challenges of Cell Culture" brought together researchers to discuss technical, methodological, and reproducibility issues in culturing melanocytes, keratinocytes, fibroblasts, and melanoma cells. The discussion between experts in the field highlighted key and recurrent pitfalls affecting experimental outcomes, including low-density seeding, temperature fluctuations, over-passaging, and mycoplasma contamination, as well as sources of variability arising from media composition, batch effects, and environmental conditions. Importantly, the workshop distinguished between practices supported by evidence and consensus-based guidance derived from collective expert experience. Species- and donor-specific differences, especially between human, mouse, and zebrafish melanocyte models, were identified as additional major determinants of experimental variability. Emerging systems, including human and mouse pluripotent stem cell (PSC)-derived melanocytes, as well as avian and zebrafish melanoma lines, were discussed for their complementary mechanistic and translational value. Overall, the workshop concluded that transparent documentation, explicit reporting standards, and shared best practices are essential to improve reproducibility and further advance pigment cell research.

The relationship between melanogenesis, pigmentation, and melanocyte behavior is complex. In melanocytes, pigmentation is often associated with differentiation, yet mature melanocytes vary in pigment content. In melanoma, pigmentation-linked transcriptional programs may have prognostic value, but visual assessments of tumor pigmentation have yielded inconsistent results. Progress linking pigmentation phenotypes to cell state has been limited by a lack of tools that can directly and dynamically quantify melanin content in live cells. Here we present QUantitative Imaging of Label-free Pigment-associated ENtities (QUILPEN), a label-free multimodal imaging technique that combines quantitative phase imaging (QPI), quadrant darkfield (QDF), and absorption imaging to independently capture light that has been transmitted, scattered, and absorbed. This nondestructive method enables live-cell imaging over multiple days without labels. We show absorption as a reliable readout of melanin content, which can be decoupled from melanosome content detected by QDF, which measures scattered light. Applying QUILPEN to melanoma cells before and during repigmentation, we find that melanin content is highly heterogeneous, and that this heterogeneity is reinstated upon repigmentation. Lineage tracking further reveals that melanin synthesis rates are heritable and can be transmitted both symmetrically and asymmetrically. QUILPEN enables real-time quantification of pigmentation dynamics and cell-level heterogeneity.

Excimer 308-nm light is often used for vitiligo treatment in combination with adjuvants. We aimed to evaluate the efficacy of these combination therapies. We searched MEDLINE, Embase and the Cochrane Library from inception to November 2024. All randomised trials reporting efficacy outcomes for vitiligo patients treated with excimer 308-nm light were included. Primary outcomes were achieving ≥ 50%, ≥ 75% and 100% skin repigmentation. Pairwise comparisons of treatment repigmentation were summarised as risk ratios (RRs) with 95% confidence intervals (CIs) and a frequentist, random-effects network meta-analysis with a graph-theoretical approach was used to generate summary estimates. Thirty-eight studies involving 1841 participants were included. Excimer 308-nm light with topical calcineurin inhibitors or topical corticosteroids significantly improved repigmentation outcomes compared to excimer monotherapy with ≥ 50% (RR 1.47, 95% CI 1.19–1.81; RR 1.65, 95% CI 1.32–2.06) and ≥ 100% repigmentation (RR 1.60, 95% CI 1.03–2.49; RR 2.31, 95% CI 1.50–3.56) respectively. Excimer in combination with topical antioxidants (RR 43.00, 95% CI 2.68–688.68), intramuscular corticosteroid (RR 1.76, 95% CI 1.13–2.74) and platelet rich plasma (RR 1.76, 95% CI 1.32–2.35) enhanced ≥ 50% repigmentation. These findings highlight the value of combination therapy with excimer light as a useful option in the management of vitiligo.