Melanoma remains challenging due to pronounced heterogeneity, early metastasis, and dynamic treatment resistance. Conventional tissue biopsy and imaging provide essential information but are limited by invasiveness, sampling bias, and an inability to capture longitudinal tumor-immune evolution. As endogenous bio-nanomaterials, small extracellular vesicles/exosomes circulate stably in body fluids and carry multi-omic cargo (DNA, RNA, proteins, lipids), enabling minimally invasive liquid biopsy and real-time disease monitoring. Beyond diagnostics, engineered exosomal nanomaterials can be functionalized and loaded with therapeutic payloads to improve targeted delivery and support combination regimens, including immunotherapy. This review highlights mechanistic roles of exosomes in melanoma progression, summarizes key liquid-biopsy biomarkers (e.g., exosomal PD-L1 and EV-miRNA/protein signatures), and discusses translational barriers such as standardization, scalable manufacturing, safety, and clinical validation.
Li Li, Xin Zheng, Jingrui Shi et al.· Microstructures· 0 citations
Background Small cell lung cancer (SCLC) is an aggressive neuroendocrine malignancy characterized by rapid proliferation, early dissemination, and limited durable benefit from current chemoimmunotherapy. Although immune checkpoint blockade has modestly improved clinical outcomes, the regulatory logic linking malignant cell states to the tumor immune microenvironment remains incompletely understood. Here, we applied an integrative single-nucleus transcriptomic framework to dissect tumor cell heterogeneity, regulatory programs, and immune-stromal communication networks in SCLC. Methods Publicly available Single-nucleus RNA sequencing data from primary and metastatic SCLC samples were analyzed using Seurat-based clustering, inferCNV-based malignant cell identification, differential expression analysis, pathway enrichment, metabolic and stemness scoring, pseudotime trajectory reconstruction, CellChat-mediated cell-cell communication inference, and transcription factor regulatory module analysis. A UBE2C-enriched proliferative tumor cell subpopulation was prioritized for functional validation. siRNA-mediated UBE2C knockdown was performed in DMS114 and NCI-H446 SCLC cell lines, followed by qRT-PCR, CCK-8, colony formation, transwell migration, and Annexin V/PI apoptosis assays. Results Using snRNA-seq, we identified multiple cell types and resolved a UBE2C+ subpopulation with marked proliferative features. UBE2C+ subpopulation displayed strong G2/M-phase enrichment, elevated mitotic and cell cycle programs. And pseudotime analysis positioned C3 UBE2C+ tumor cells at a proliferative state during tumor cell state evolution. Cell-cell communication analysis suggested that this subpopulation might interact with macrophages and fibroblasts through GRN-SORT1 and THBS1-CD47/CD36 signaling axes, indicating a potential link between proliferative tumor states and candidate communication axes. Transcription factor module analysis further revealed enrichment of cell cycle-associated regulators, including MYBL2, NFYB, E2F2, TGIF1, and RXRG, in the C3 subpopulation. Functionally, UBE2C knockdown significantly suppressed proliferation, clonogenic growth, and migration while increasing apoptosis in SCLC cells. Conclusions This study identified UBE2C+ proliferative tumor cells as a functionally relevant malignant subpopulation in SCLC and links this state to immune-stromal communication networks within the tumor microenvironment. By integrating single-nucleus transcriptomics, regulatory network inference, intercellular communication analysis, and in vitro validation, our findings nominate UBE2C as a potential candidate functional regulator and provide a systems-level framework for investigating the cancer-immunity regulome in SCLC.
Hong-Ling Jia, Yongxuan An, Bing Chen et al.· Frontiers in Immunology· 0 citations
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