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The paracrine effects of tumor-resident mesenchymal stem/stromal cells in the microenvironment of brain metastases.

BACKGROUND: Tumor-resident mesenchymal stem/stromal cells (MSCs) were identified in several cancers, and were implicated in regulating multiple aspects of tumor progression. However, the role of tumor-resident MSCs in the pathophysiology of brain metastases (BrMs) -the most prevalent type of malignant brain tumor- is currently unknown, and was investigated in this study. METHODS: Tumor-resident MSCs were isolated from fresh human lung-BrM tissues (n=3) and were phenotypically assessed in FFPE lung-BrM tissues (n=11). The paracrine effects of BrM-MSCs on neutrophil granulocytes and endothelial

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… However, accumulating evidence indicates that MSCs also reside directly in the tumor microenvironment (TME) (reviewed in ( 8 , 9 )). … TLR4 signaling drives mesenchymal stromal cells commitment to promote tumor microenvironment transformation in multiple myeloma (vol 10, 704, 2019) . …

Single-cell and spatial transcriptomics analyses reveal tumor microenvironment-driven proliferation of NF2-associated vestibular schwannomas.

The tumor microenvironment (TME) is crucial for tumor formation and progression, but its specific impact on NF2-related tumors has not been well described. The aim of this study was to analyze the differences in the TME among NF2-related schwannomatosis (NF2-SWN) patients with different clinical phenotypes, explore the reasons for these differences, and identify targets for treatment while gaining a deeper understanding of the pathogenesis of the disease. 20 vestibular schwannomas (VSs) from 20 clinically diagnosed NF2-SWN patients, including 11 milder patients (Gardner) and 9 severe patients …

Role of WDR66 in Stemness, Therapy Resistance and Tumor microenvironment modulation in Head and Neck Cancer.

Head and neck cancer comprises a variety of malignant tumors affecting regions such as the oral cavity, pharynx, larynx, paranasal sinuses, … o cisplatin. These effects were more pronounced in vivo, suggesting a relevant role of WDR66 in the tumor microenvironment. The medium conditioned by cells overexpressing WDR66 promoted migration, maintained the stem cell phenotype, and inhibited immune differentiation, harboring soluble factors involved in progression and metastasis. In this media, we identified severa …

Shaoyao Decoction Inhibits Colorectal Cancer Progression by Targeting PD-L1 to Reprogram the Immunosuppressive Tumor Microenvironment.

Colorectal cancer (CRC), particularly the microsatellite-stable (MSS) subtype accounting for ~ 85% of cases, remains refractory to immune ch … ollectively, SYD exerts potent anti-CRC effects by targeting PD-L1 to remodel the immunosuppressive tumor microenvironment. As a multi-target agent, it holds great promise for MSS-CRC, bridging TCM with modern immuno-oncology.

Stealthy systemic circulation of spatially controlled tumor microenvironment-activated bioadhesive proteinic nanoparticles for pancreatic cancer chemotherapy.

Pancreatic cancer remains one of the deadliest malignancies, largely due to late diagnosis and the limited efficacy of systemic chemotherapy. Here, we propose a tumor microenvironment-activated bioadhesive nanoparticle platform designed to enhance intratumoral drug retention and therapeutic efficacy following systemic intravenous administration. The system was based on bioengineered mussel adhesive protein (MAP)-derived nanoparticles that were conjugated with polyethylene glycol (PEG) shielding linked via a matrix metalloproteinase-2 (MMP2)-cleavable peptide, enabling stealth systemic circulat…

Crosslink Between Neuroinflammation and Oxidative/Nitrosative Status in the Glioblastoma Tumor Microenvironment: Prognostic and Theranostic Impact.

Glioblastoma (GB) is the most aggressive primary brain tumor, characterized by rapid progression, therapeutic resistance, and poor prognosis. Increasing evidence suggests that oxidative and nitrosative stress, together with a proinflammatory tumor microenvironment (TME), play a critical role in gliomagenesis. In this study, we analyzed a cohort of 89 Algerian patients with GB glioblastoma, to characterize systemic and intratumoral oxidative/ nitrosative status. Hydrogen peroxide, malondialdehyde, total nitrite levels, and catalase activity were quantified in serum or plasma, cystic fluid, and …

Tumor microenvironment and its implications for atomic force microscopy-based nanomechanics of cancer cells: a perspective.

Forces are crucial for regulating physiological and pathological processes, and in particular, the mechanical phenotype of cancer cells has … contributions to the field of cancer mechanobiology. Concurrently, it is increasingly apparent that tumor microenvironment is not a passive bystander but plays a pivotal role in shaping cancer cell functions and promoting tumor development. Nevertheless, the effect of the tumor microenvironment on cancer cell mechanics has long been omitted in experiments utilizing AFM …

Bladder cancer precision-cut tumor slices (PCTS) preserve functional immune microenvironment enabling ex vivo drug evaluation.

BACKGROUND: The development of effective cancer immunotherapies is hindered by the lack of preclinical models that faithfully preserve tumor … versatile human-derived tool for evaluating cancer immunotherapies while maintaining physiological tumor microenvironment complexity. The technical foundation established here enables future prospective studies correlating ex vivo responses with patient clinical outcomes, potentially advancing personalized treatment selection and reducing reliance on animal models in i …

From peripheral blood to tumor microenvironment: spatial dimension deficiency and paradigm reconstruction in immunotherapy biomarker research.

Immunotherapy biomarker research has long relied on peripheral blood as the main sample source. However, significant spatial heterogeneity exists between peripheral blood and the tumor microenvironment (TME). This perspective article proposes that the core limitation of current biomarker studies is not throughput or omics technology, but rather the incomplete integration of spatial information. We scrutinize the phenomenon of "spatial decoupling" between peripheral blood and the TME in terms of immune composition, dynamic responses, and clinical predictive performance. It is evident that blood…

Neuro-immune interactions in colorectal cancer: mechanistic insights and therapeutic implications within the tumor immune microenvironment.

Within the CRC microenvironment, neural and immunological systems constitute a regulatory axis with strong dynamism and bidirectionality, thereby profoundly influencing tumor initiation, immune evasion, and therapeutic resistance. Here, we systematically outline the anatomical as well as functional underpinnings, the molecular mechanisms, and the translational potential of neuro-immune crosstalk within CRC. A unique biological context is offered by the gut, which houses two key components: an autonomous "second brain", namely the enteric nervous system (ENS), and the human body's largest immun

Single-Cell Transcriptomic Analysis Reveals Ferroptosis-Related Signatures and Tumor Microenvironment Heterogeneity in Epithelial Ovarian Cancer.

Epithelial ovarian cancer (EOC) is the deadliest gynecological malignancy. Ferroptosis, an iron-dependent lipid peroxidation-associated cell death mode, provides a new target for tumor therapy. Nevertheless, its impact on EOC tumorigenesis is not well defined. The quality control, dimensionality reduction, and EOC clustering for the gene expression data were performed through the Scanpy pipeline for single-cell RNA sequence from GEO (GSE165897). Ferroptosis pathway scoring, computation of transcription factor activity, and analyzes for cell-cell communication were conducted. An independent val

Age and sex: dual drivers remodeling the anti-tumor immune microenvironment and shaping personalized immuno-oncology.

Despite breakthrough advancements in cancer immunotherapy, significant inter-individual heterogeneity in clinical outcomes persists, bringin … senescence-associated secretory phenotype (SASP) orchestrate the formation of an immunosuppressive tumor microenvironment. In the dimension of sex, we deeply explore four core mechanisms comprising sex chromosome genomics (e.g., escape from X-chromosome inactivation and loss of Y chromosome), sex hormone networks, microenvironmental metabolic reprogramming, and the hos …

Paracrine Orchestration of Tumor Microenvironment Remodeling Induced by GLO1 Potentiates Lymph Node Metastasis in Breast Cancer.

Breast cancer is the most prevalent form of malignant tumor that frequently metastasizes to axillary lymph nodes (LNs). Nonetheless, the precise mechanisms underlying alterations in the tumor microenvironment (TME) in LN metastasis in breast cancer remain poorly understood. Single-cell RNA sequencing of 28 LN samples from 23 patients is performed, and a comprehensive landscape of the entire ecosystem is generated. Ten major cell types are identified, with the subclusters of each major cell type exhibiting diverse characteristics. Furthermore, multiple signatures are collected to evaluate the k…

Identification of a tumor microenvironment-related gene signature for predicting prognosis in patients with gastric cancer.

Tumor microenvironment (TME) plays an important role in the prognosis of gastric cancer (GC). The aim of this study was to identify a TME-related gene signature and provide a basis for prognosis evaluation of GC. X-cell and cluster analyses were performed on 373 tumor samples from The Cancer Genome Atlas-Stomach Adenocarcinoma. Prognostic-related genes were screened using differential analysis. Univariate Cox analysis, LASSO regression, and multivariate Cox analysis were used to determine the candidate genes and construct the prognostic model. Independent prognostic and correlation analyses of…

Perineural invasion and the "cold" tumor microenvironment in pancreatic cancer: mechanisms of crosstalk and therapeutic opportunities.

Pancreatic ductal adenocarcinoma (PDAC) remains a devastating malignancy characterized by profound lethality, aggressive local invasion, dismal prognosis, and significant resistance to existing therapies. Two critical biological features underpin the challenges in treating PDAC: extensive perineural invasion (PNI), the process by which cancer cells infiltrate and migrate along nerves, and a profoundly immunosuppressive, or "cold," tumor microenvironment (TME). PNI is not only a primary route for local tumor dissemination and recurrence but also a major contributor to the severe pain often expe…

Exploring TROP2 expression in oropharyngeal squamous cell carcinoma: Association with prognosis and tumor immune microenvironment composition.

Oropharyngeal squamous cell carcinoma (OPSCC) presents prognostic and therapeutic challenges. Trophoblast cell surface antigen 2 (TROP2) is … le pathologic characteristics, improved DFS, and a higher presence of cytotoxic immune cells in the tumor microenvironment.

Decoding tumor-infiltrating lymphocytes heterogeneity in ductal carcinoma in situ: immune microenvironment dynamics and prognostic insights.

With the widespread use of mammography, the incidence of ductal carcinoma in situ (DCIS) has significantly increased and currently accounts for approximately 20-25% of newly diagnosed breast cancer cases. While a significant proportion of DCIS lesions exhibit long-term indolence without progression to invasive carcinoma, the current paucity of validated biomarkers for invasive potential prediction creates a therapeutic dilemma in clinical practice, potentially leading to either overtreatment of biologically inert lesions or undertreatment of high-risk precursors. Reflecting the body's adaptive

Insights into the Mechanisms of Immune-Checkpoint Inhibitors Gained from Spatiotemporal Dynamics of the Tumor Microenvironment.

Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has revolutionized cancer treatment, yet durable responses are achieved in only a subset of patients. The tumor microenvironment (TME) plays a key role in cancer progression and immune modulation, critically influencing the efficacy of ICIs. Recent advances in single-cell technologies have enabled high-resolution profiling of the TME, particularly tumor-infiltrating immune cells, across diverse cancer types. However, our understanding of how immune cells shape ICI responses and how they are dynamically altered during treatment re…

The Role of Fibroblasts in Melanoma Development: From Tumor Microenvironment Remodeling to Pre-Metastatic Niche Formation.

Melanoma is the most aggressive form of skin cancer, and despite significant therapeutic advances over the past decade, a substantial number of patients still progress to a fatal outcome. The initiation and progression of melanoma are strongly influenced by interactions between melanoma cells and other components of the tumor microenvironment (TME). In this review, we focus on the interplay between fibroblasts resident in the tumor microenvironment and tumor cells. In particular, we examine the molecular mechanisms through which melanoma cells induce the transformation of resident fibroblasts …

Tumor Microenvironment-Responsive Nanocluster for Time-Resolved Hyperthermic Intraperitoneal Chemo/Thermal-Therapy against Colorectal Peritoneal Metastasis.

Peritoneal metastasis (PM) originating from gastrointestinal cancer was considered a terminal disease until recently. It poses significant therapeutic challenges due to its diffuse nature and barriers to effective drug delivery. While locoregional approaches such as hyperthermic intraperitoneal chemotherapy (HIPEC) extend survival, their efficacy is constrained by systemic toxicity and tumor thermoresistance. To address these issues, we developed a tumor microenvironment-responsive nanocluster system (MoNs@MyC) for augmented HIPEC treatment. Comprising ultrasmall monodispersed-nanoclusters (Mo…