Skin cutaneous melanoma (SKCM) is a highly aggressive malignancy originating from melanocytes, with a continuously rising global incidence. Developing strategies for early prevention and precise treatment remains a major challenge in oncology. Notably, advances in immunotherapy have brought new hope to SKCM patients. Increasing evidence suggests that various forms of regulated cell death, particularly cuproptosis and ferroptosis, can modulate the tumor microenvironment (TME) by inducing the death of both tumor and immune cells, thereby influencing the efficacy of immunotherapy. Consequently, there is a critical need to establish methods for early diagnosis and to develop reliable prognostic models prognostic models based on immune-related biomarkers.

We integrated RNA sequencing data and corresponding clinical information from SKCM patients obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Using single-cell transcriptomic data from the GSE72056 dataset, we analyzed the expression patterns of cuproptosis-ferroptosis-related genes (CFRGs) in SKCM and their enrichment in immune cell subsets. Key CFRG features were screened using machine learning algorithms to construct a prognostic risk-scoring model, which demonstrated robust predictive performance across multiple independent cohorts. Furthermore, we explored the associations between core CFRGs and patient survival outcomes, immunotherapy response, and drug sensitivity in SKCM.

We identified 10 key genes that were significantly associated with SKCM survival and successfully constructed a machine learning-based prognostic prediction model. This model showed strong predictive performance and demonstrated superior accuracy compared with existing prognostic models, as supported by cross-cohort and cross-cancer validation. Four key genes (IFNG, PTPN6, SLC38A1, and SOCS1) were further identified through association analyses with clinical phenotypes and showed significant correlations with clinical characteristics. Distinct immune cell infiltration patterns were observed between high- and low-risk groups stratified by these genes, indicating marked heterogeneity within the TME. This heterogeneity may directly influence patient responses to immunotherapy. Additionally, molecular docking analyses identified several potential therapeutic compounds, among which selumetinib demonstrated strong binding affinity to the target proteins IFNG, PTPN6, and SOCS1, suggesting a potential therapeutic strategy for advanced SKCM.

IFNG, PTPN6, SLC38A1, and SOCS1 may serve as potential biomarkers of poor prognosis in SKCM patients. These genes demonstrate predictive value for immunotherapy response and drug sensitivity, particularly indicating susceptibility to selumetinib treatment, and therefore show substantial potential for clinical translation.

Ramsay Hunt syndrome (RHS) typically presents with unilateral otalgia, herpes zoster oticus, ipsilateral peripheral facial palsy, and often ipsilateral vestibulocochlear involvement. Bilateral/contralateral vestibular dysfunction is extremely rare.

A 60-year-old female with a history of right breast cancer presented to our clinic with 1 week of vertigo, followed by 2 days of right-sided facial deviation and otalgia. Physical examination revealed vesicular eruptions around the right ear and external auditory canal, right-sided peripheral facial palsy, spontaneous horizontal-rotatory nystagmus (with a fast phase to the left), and postural instability. Further evaluation confirmed bilateral vestibular hypofunction: the video head impulse test showed reduced gains and/or saccades in all canals; bithermal caloric testing demonstrated bilateral vestibular weakness (sum of slow-phase velocity: 10.1°/s); and symptom assessments yielded a visual analog scale (VAS) score of 7/10 and a dizziness handicap inventory (DHI) total score of 52. Facial nerve electrophysiological testing indicated significant impairment of the right facial nerve, with an amplitude reduction exceeding 50%. The stapedial reflex, Hallpike-Dix test, Roll test, pure-tone audiometry, brain and cranial nerve MRI, and routine laboratory tests showed no significant abnormalities. A diagnosis of RHS with bilateral vestibular dysfunction was established, and treatment was administered per current guidelines, including antiviral therapy, oral corticosteroids, analgesics, anti-vertigo medications, acupuncture, and vestibular rehabilitation. After 2 weeks, symptoms (facial palsy, otalgia, herpes zoster, and dizziness) improved slightly, with crusting of the herpes lesions. At the 3-month follow-up, the herpes zoster had resolved without residual pain, though mild residual dizziness (VAS 2, DHI 20) and facial weakness persisted.

This case shows rare bilateral vestibular involvement and initial vestibular impairment preceding RHS (distinct from classical ipsilateral or rare post-RHS contralateral patterns). Elucidating the specific pathogenic mechanisms underlying this presentation holds significant clinical importance for understanding bilateral vestibular involvement.

Arising from extracranial cancers, brain metastases (BrM) are the most prevalent brain malignancy in adults. Even though there are recent advances in systemic cancer therapies and immunotherapies, the prognosis for BrM remains poor, with median survival rather dismal. The central nervous system (CNS) presents a distinct immunological and structural landscape that restricts immune surveillance and effective therapeutic delivery. This immune privilege is enforced by the blood brain barrier (BBB), specialized myeloid populations, in conjunction with reduced lymphatic drainage, which collectively constrains the effector immune cell trafficking and antigen presentation. Thus, immunotherapeutic strategies that have revolutionized systemic oncology, such as immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR)-T cell therapies, have presented only rather modest benefit in BrM. While immunotherapy-focused research has largely focused on T-cell-mediated mechanisms, an accumulation of recent findings suggest that B cells play multifaceted and underexplored roles within the unique CNS tumor microenvironment (TME). Aside from antibody production, B cells contribute to antigen presentation, cytokine secretion, and the formation of tertiary lymphoid structures which are functions that can either promote or suppress antitumor immunity depending on their differentiation state and local cues. In primary brain tumors, like glioblastoma (GBM), B cell infiltration has been linked to both enhance immune activation and immune regulation, yet their significance in BrM remains comparatively undefined. Understanding how B cells adapt and function within the niche constraints of the CNS, such as how they influence immune suppression, antigen presentation, and TME remodeling, may reveal new therapeutic vulnerabilities and allow for harnessing complementary B cell-based immunotherapies instead of T cell-focused approaches. This review synthesizes current knowledge on the structural and immunological features that differentiate BrM from primary brain tumors and extracranial metastases. We highlight the emerging evidence on B cell biology in the CNS, and discuss their immunostimulatory and immunoregulatory capacities, while exploring ongoing efforts to leverage B cell-based immunotherapies in brain malignancies, specifically proposed BrM. By defining the immunological landscape of BrM and the therapeutic promise of B cells, this work suggests a new possibility in CNS oncology, where humoral immunity may be harnessed to target brain metastatic malignancies.

Cancer remains a major global health challenge, and although immunotherapy has achieved remarkable breakthroughs, its efficacy is often limited by tumor-induced immunosuppression within the tumor microenvironment (TME). Emerging evidence indicates that metabolic reprogramming plays a pivotal role in shaping the TME and regulating antitumor immune responses. Targeting tumor and immune cell metabolism has therefore become a promising strategy to enhance the effectiveness of cancer immunotherapy. This review first summarizes the metabolic reprogramming that occurs within the TME, including alterations in glucose, lipid, and amino acid metabolism in tumor cells, as well as the metabolic adaptation of immune cells. We then highlight recent advances in natural products that modulate key metabolic pathways and their potential to reshape the immunosuppressive TME. Special emphasis is placed on natural compounds that not only inhibit tumor cell metabolism but also restore the metabolic fitness of immune cells, thereby improving antitumor immunity. In addition, advances in delivery strategies, including nanocarrier-based and stimuli-responsive systems, are reviewed for their roles in improving the bioavailability, stability, and tumor targeting of natural metabolism-regulating agents. Finally, we discuss the current status and challenges of translating natural metabolism-regulating agents into clinical applications, including issues of dose optimization, safety evaluation, and patient selection. Despite these hurdles, precision targeting of metabolic pathways, interdisciplinary collaboration, and the discovery of novel compounds-particularly immune-sensitizing agents derived from traditional medicine-are expected to accelerate progress. Collectively, natural products represent promising adjuvant strategies for cancer immunotherapy, with great potential to overcome current therapeutic limitations and improve clinical outcomes.

Tissue inhibitor of metalloproteinase 1 (TIMP1) plays diverse roles in extracellular matrix (ECM) remodeling, immune regulation, and tumor progression. However, its systemic patterns across cancers and cardiovascular disease remain incompletely understood.

We applied an integrative pipeline beginning with microarray analysis of tumor-bearing mouse hearts (GSE63032) to identify TIMP1 as a hub gene. Pan-cancer datasets from TCGA/GTEx and public portals were analyzed for expression, genomic alterations, epigenetic regulation, immune infiltration, prognosis, and drug sensitivity. Single-cell RNA-seq was used to define cell type-specific expression. As all large-scale analyses were performed using publicly available bioinformatics datasets, cell line experiments were used for targeted validation of TIMP1 expression and function. Findings were validated by immunohistochemistry, western blotting, and transwell assays in colorectal and gastric cancer models, with additional analysis performed in atherosclerosis cohort (GSE100927) and heart failing cohort (GSE5406) to explore cardiovascular relevance.

TIMP1 was consistently upregulated across cancers, especially in colorectal and gastric tumors, where it correlated with adverse survival and high diagnostic accuracy. Genomic analyses revealed copy number alterations, while promoter hypomethylation aligned with increased expression in digestive cancers. Drug-response profiling indicated sensitivity to epigenetic inhibitors and resistance to MAPK-targeted agents. Single-cell analyses localized TIMP1 to myeloid cells in colorectal cancer and fibroblasts in gastric cancer, linking it to apoptosis, EMT, angiogenesis, and stromal-immune crosstalk. Beyond oncology, TIMP1 was elevated in atherosclerosis, aligning with immune- and lipid-related pathways, but reduced in heart failure, where it was linked to impaired mitochondrial metabolism.

This multi-level and bioinformatics study identifies TIMP1 as a cross-disease regulator with context-dependent functions. TIMP1 serves as a potential prognostic and diagnostic biomarker in digestive cancers, a therapeutic stratification marker for epigenetic interventions, and a candidate mediator linking tumor biology with cardiovascular disorders such as atherosclerosis and heart failure.

Ovarian cancer (OC), particularly epithelial ovarian cancer (EOC), represents one of the most lethal and aggressive gynecological malignancies. Despite advances in surgery, chemotherapy, and immunotherapy, patient survival remains poor. Identifying novel molecular targets is crucial for improving early diagnosis and developing more effective therapies.

We examined the expression and immunoregulatory function of SLC40A1 in EOC using both experiments on cells and mouse orthotopic tumor models. Through integrated in vitro and in vivo studies, we systematically assessed the role of SLC40A1 in promoting M1 macrophage polarization and its relationship with tumor suppression, demonstrating that SLC40A1 enhances the response to immunotherapy.

SLC40A1 was found to be more highly expressed in normal ovarian tissues compared with EOC tissues, and its high expression was associated with a favorable prognosis. In vitro, SLC40A1 did not significantly affect tumor cell proliferation, apoptosis, or migration and invasion. However, in vivo experiments using mice with differing immune status demonstrated that SLC40A1 modulates the tumor immune microenvironment. Subsequent bioinformatics analyses suggested that SLC40A1 may regulate M1 macrophage polarization. Mechanistically, in vitro experiments confirmed that SLC40A1 regulates CXCL11 secretion, which activates the JAK2-STAT1 signaling pathway, promoting macrophage TNF-α production, which in turn upregulates SLC40A1 expression. Finally, we demonstrated that SLC40A1 enhances the response to immunotherapy.

These findings identify SLC40A1 as a key regulator of the antitumor immune response in EOC. High SLC40A1 expression is associated with enhanced macrophage-mediated tumor suppression and improved response to immunotherapy, highlighting its potential as both a prognostic biomarker and a therapeutic target.

Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer, is a genetic condition that increases the risk of developing colorectal cancer (CRC) and other cancers due to defective DNA mismatch repair (dMMR). This article reports a case of a patient who developed lung adenocarcinoma followed by CRC. The detection of dMMR by immunohistochemistry in both the metastatic lesion and CRC led to retrospective testing, which revealed a concomitant loss of MLH1 and PMS2 in the primary lung cancer. Germline testing subsequently confirmed a diagnosis of LS associated with an MLH1 mutation, with significant familial clustering observed. The patient responded effectively to anti-PD-1 immunotherapy. This case highlights that lung adenocarcinoma can be a manifestation of LS and underscores the critical importance of retrospective MMR testing in establishing the diagnosis. Furthermore, it demonstrates the efficacy of immune checkpoint inhibitions in advanced dMMR tumors.

As high-throughput sequencing tools have advanced in recent years, scientists have discovered that lung cancer tissues are not sterile. The intratumoral microbiota exists in the tumor parenchyma and stroma in a low-biomass form. This finding has overturned the traditional concept of "sterile tumors" and brought the intratumoral microbiota to the forefront of tumor research. In this review, we focus on elucidating the mechanisms by which intratumoral microbiota influence lung cancer cells and the tumor microenvironment (TME), with the aim of clarifying their role in lung cancer progression. The intratumoral microbiota does not exist as a passive resident. Instead, it may actively induce and maintain a chronic inflammatory state through the secretion of metabolites, activation of signaling pathways, immune suppressor cell recruitment, and upregulation of immune checkpoint molecule expression, thereby promoting tumor cell proliferation, invasion, and immune evasion. From a clinical translation perspective, we explore the potential of using intratumoral microbiota characteristics to predict immunotherapy efficacy. Additionally, we assess the application prospects of engineered bacteria and targeted nanobiotics, which are based on synthetic biology, in reshaping the immune microenvironment. However, the field still faces significant challenges, particularly as the low biomass nature of lung tissues makes sequencing data highly susceptible to reagent contamination and batch effects. Additionally, the synergistic role of non-bacterial components such as fungi and viruses in the tumor ecosystem is often overlooked. Future research needs to establish rigorous quality control standards and integrate multi-omics technologies to comprehensively analyze the dynamic interaction network between the microbiota and host immunity, which will drive the clinical implementation of microbiome-based precision diagnostic and therapeutic strategies for lung cancer.

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, with limited efficacy of current therapies in advanced cases. As a key risk factor for HCC, liver fibrosis may influence tumor progression and immune responses. However, fibrosis-related therapeutic targets remain poorly defined. This study aimed to identify fibrosis-related genes in HCC tumor microenvironment (TME).

Our research integrated single-cell RNA sequencing (GSE149614), spatial transcriptomics (GSE245908), and bulk RNA-seq data to identify fibrosis-related prognostic genes in HCC. The genes were selected via the Random Survival Forest algorithm. Additionally, bioinformatics analyses were conducted to explore gene expression patterns, immune infiltration, and spatial localization. Key genes were further validated through in EDU incorporation assay, Transwell migration assay, and CCK-8 proliferation assay.

Firstly, single-cell analysis identified endothelial cells as key fibrosis-associated cluster in HCC. Three fibrosis-related prognostic genes, LUC7L3, CREB1, and YIPF4, were further identified and validated to patient survival, immune infiltration, and metabolic activity. In addition, enrichment and drug sensitivity analyses linked key genes to tumor-related pathways and chemotherapy response. Spatial transcriptomics then confirmed the spatial distribution and interactions of these genes. Lastly, cellular assays showed that YIPF4 promoted proliferation and migration of HCC cells.

In this study, we identified fibrosis-related prognostic genes in HCC, including LUC7L3, CREB1, and YIPF4. The roles of these genes in TME were further explored through relevant analyses, potentially providing clinical evidence to support decision-making in HCC management.

Glioma is a highly heterogeneous and aggressive malignancy of the central nervous system, and reliable molecular biomarkers are urgently needed to improve prognostic stratification and guide therapeutic decision-making. The MEX3 family of RNA-binding proteins has been implicated in tumorigenesis and post-transcriptional regulation; however, their comprehensive roles in glioma remain poorly understood.

Integrated bioinformatic analyses were performed using transcriptomic and clinical data from TCGA, CGGA, and GEO cohorts to evaluate the expression profiles, diagnostic and prognostic value, genetic alterations, molecular interactions, immune infiltration characteristics, and functional pathways associated with MEX3A, MEX3B, MEX3C, and MEX3D. Protein-protein interaction networks, gene set enrichment, and co-expression analyses were conducted to explore potential biological mechanisms. A MEX3-related prognostic risk model was constructed and validated in independent datasets. Drug sensitivity correlations were analyzed using public pharmacogenomic resources. In addition, in vitro experiments, including qRT-PCR, western blotting, proliferation, migration, and invasion assays, were performed in U251 and LN229 glioma cell lines to functionally validate the bioinformatic findings.

All four MEX3 family members were significantly upregulated in glioma tissues compared with normal controls and demonstrated strong diagnostic performance. Distinct prognostic patterns were observed, with MEX3D consistently identified as an independent predictor of poor overall, disease-specific, and progression-free survival. MEX3 genes were associated with diverse genetic alterations and were enriched in pathways related to RNA processing, cell cycle regulation, and cancer-associated signaling. Immune analyses revealed significant correlations between MEX3 expression and multiple immune cell populations as well as immune checkpoint molecules, suggesting potential roles in shaping the glioma immune microenvironment. A MEX3-related co-expression-based prognostic model showed robust survival-predictive ability and remained effective in external validation cohorts. Functional assays confirmed that silencing individual MEX3 genes significantly inhibited glioma cell proliferation, migration, and invasion in vitro.

This study provides a comprehensive characterization of the MEX3 family in glioma, demonstrating their dysregulation, prognostic relevance, immune associations, and functional contributions to malignant phenotypes. Among them, MEX3D emerges as a particularly promising prognostic biomarker. These findings establish a foundation for future mechanistic and translational studies exploring MEX3 family members as potential biomarkers or therapeutic targets in glioma.