Результаты поиска

Combination of radiation and interleukin 12 eradicates large orthotopic hepatocellular carcinoma through immunomodulation of tumor microenvironment.

Immunotherapies have shown promising results in certain cancer patients. For hepatocellular carcinoma (HCC), the multiplicity of an immunotolerant microenvironment within both the tumor, and the liver per se may limit the efficacy of cancer immunotherapies. Since radiation induces immunogenic cell death and inflammatory reactions within the tumor microenvironment, we hypothesized that a combination therapy of radiation and lasting local immunostimulating agents, achieved by intratumoral injection of an adenoviral vector encoding interleukin 12, may reverse the immunotolerant microenvironment w…

Prognostic and predictive aspects of the tumor immune microenvironment and immune checkpoints in malignant pleural mesothelioma.

Malignant pleural mesothelioma (MPM) is an aggressive cancer with a poor prognosis and an increasing incidence, for which novel therapeutic strategies are urgently required. Since the immune system has been described to play a presumed role in the protection against MPM, characterization of its tumor immune microenvironment (TME) and immune checkpoints can identify new immunotherapeutic targets and their predictive and/or prognostic value. To characterize the TME and the immune checkpoint expression profile, we performed immunohistochemistry (IHC) on formalin-fixed paraffin embedded (FFPE) tis

Impact of stromal cell components of tumor microenvironment on epithelial-mesenchymal transition in breast cancer cells.

BACKGROUND: Cell and tissue homeostasis results from the dynamic balance of cell - cell and cell - extracellular component crosstalk that re … egration cell system for investigation of the mechanisms of interaction between tumor cells and the tumor microenvironment in vitro was developed. The significant changes in proliferative activity of TC dependently on its -ЕМT-status were detected after their interaction with fibroblasts and endothelial cells in noncontact co-cultivation system. BM cells of BC patients …

CD90+ mesothelial-like cells in peritoneal fluid promote peritoneal metastasis by forming a tumor permissive microenvironment.

The peritoneal cavity is a common target of metastatic gastrointestinal and ovarian cancer cells, but the mechanisms leading to peritoneal metastasis have not been fully elucidated. In this study, we examined the roles of cells in peritoneal fluids on the development of peritoneal metastasis. We found that a minor subset of human intraperitoneal cells with CD90(+)/CD45(-) phenotype vigorously grew in culture with mesothelial-like appearance. The mesothelial-like cells (MLC) displayed the characteristics of mesenchymal stem cell, such as differentiating into adipocytes, osteocytes, and chondroc

An osteoblast-derived proteinase controls tumor cell survival via TGF-beta activation in the bone microenvironment.

BACKGROUND: Breast to bone metastases frequently induce a "vicious cycle" in which osteoclast mediated bone resorption and proteolysis results in the release of bone matrix sequestered factors that drive tumor growth. While osteoclasts express numerous proteinases, analysis of human breast to bone metastases unexpectedly revealed that bone forming osteoblasts were consistently positive for the proteinase, MMP-2. Given the role of MMP-2 in extracellular matrix degradation and growth factor/cytokine processing, we tested whether osteoblast derived MMP-2 contributed to the vicious cycle of tumor

Selective serotonin reuptake inhibitor fluoxetine, reduces solid tumor burden and metastasis through activation of host antitumor immune response and modulation of tumor microenvironment.

The tumor microenvironment (TME) plays a pivotal role in tumorigenesis, metastasis, and resistance to therapy. Although immunotherapeutic approaches such as CAR-T cells, immune checkpoint inhibitors, and tumor vaccines have demonstrated promising therapeutic effectiveness, tumor heterogeneity and immunosuppression continue to limit their efficacy in solid tumors, therefore, development of effective low-cost TME targeted therapy is necessary. Recent studies indicate, selective serotonin reuptake inhibitors display immune modulatory effects. Fluoxetine is an US Food and Drug Administration-appro…

Tumor-Specific Delivery of CD28 siRNA via Lyso-PC C-16 Modified Lipid Nanoparticles Overcomes Anti-PD-1 Resistance by Remodeling Tumor Microenvironment.

Uncovering novel targets that synergize with immune checkpoint blockade (ICB) is an urgent clinical priority. While cancer cell-intrinsic CD … commercial lipid formulations. Consequently, targeted Cd28 silencing reshapes the immunosuppressive tumor microenvironment, augmenting twofold CD8+ T cell infiltration and dendritic cell activation to extend survival in murine breast and lung cancer models to 1.3-1.5 folds. Furthermore, the combined use of LPC-LNP-Cd28 effectively eradicates resistance to anti-PD-1 ther …

Monocarboxylate Transporter 2 (MCT2) Reduction Is Associated with Increased Lung Tumor Growth and Alterations in the Immune Microenvironment in a Subcutaneous Tumor Model.

Monocarboxylate transporter 2 (MCT2; SLC16A7) is a high-affinity pyruvate transporter implicated in cancer metabolism. However, its role in lung cancer progression and the tumor microenvironment remains unclear. This study examined the effects of MCT2 reduction on tumor growth and cell-type-specific transcriptional changes within the tumor microenvironment. MCT2 loxP/loxP mice were crossed with mCre-Tg mice, and MCT2 deletion was induced by tamoxifen. Control (CO) mice received vehicle treatment. TC1 cells (100,000 cells/mouse) were injected subcutaneously, and tumors were harvested after 24 d…

VP3.15, двойной ингибитор GSK-3β/PDE7, уменьшает рост опухоли глиобластомы, изменяя микроопухоль в контексте PTEN дикой природы.

Глиобластома (ГБ) — неизлечимый рак мозга, и необходимо срочно определить эффективные методы лечения. Это может быть достигнуто либо путем идентификации новых молекул, либо путем переочистки наркотиков. Для определения терапевтического потенциала известных ингибиторов GSK-3β и/или PDE7 в GB был проведен анализ наркотиков с использованием модели глиомы Дрософила меланогастера. VP3.15, двойной ингибитор с противовоспалительными и нейрозащитными функциями при множественном склерозе, был выбран для дальнейшего изучения. VP3.15 продемонстрировал высокую антиопухоль против панели клеток человека и м

Совпадение в полном тексте источника
… As this molecule disrupts the supportive tumor microenvironment, tumors are likely to be less susceptible to the emergence of resistant subclones with different genetic alterations. …

Heterogeneity of tumor immune microenvironment of EGFR/ALK-positive tumors versus EGFR/ALK-negative tumors in resected brain metastases from lung adenocarcinoma.

BACKGROUND: Previous studies found that lung adenocarcinomas (LUAD) with EGFR-positive and ALK-positive were less responsive to immunotherap … K-positive tumors present a relatively immunosuppressive microenvironment, but the heterogeneity of tumor microenvironment may undergo different mechanisms. EGFR-positive BMs showed decreased CD8+T cells and increased regulatory T cells (Treg) cells, while ALK-positive BMs showed decreased CD8+T cells and increased M2 macrophages. Moreover, in the TCGA-LUAD cohort, EGFR …

Multi-omics analysis of the mechanism by ATP13A2 regulates the tumor microenvironment and prognosis in hepatocellular carcinoma.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is a prevalent global cancer. Most patients with HCC are diagnosed at an advanced stage. … scRNA-seq analysis demonstrated that ATP13A2 + malignant cells exhibited stronger interactions with tumor microenvironment (TME) cells. stRNA-seq analysis revealed that ATP13A2 + malignant cells were significantly spatially correlated with TME cells. The DeepSurv prognostic model indicated that HCC patients with high risk scores had a significantly lower survival rate t …

Single-cell sequencing reveals the functional heterogeneity of melanoma cells and their crosstalk with the tumor microenvironment.

BACKGROUND: Cutaneous melanoma is a highly aggressive malignancy characterized by significant heterogeneity, rapid progression, and variable treatment responses. Understanding the functional diversity of melanoma cells and their interactions with the tumor microenvironment (TME) is crucial for developing effective therapeutic strategies and identifying prognostic biomarkers. METHODS: We performed comprehensive single-cell RNA sequencing (scRNA-seq) analysis of 70,760 cells from 11 melanoma samples. Data processing was conducted using Seurat v4.3.0 with Harmony integration. Cell-cell communica…

MicroRNAs and immunotherapy in testicular germ cell tumors: opportunities and challenges for modulation of the immune microenvironment.

Testicular germ cell tumors (TGCTs) are the most common solid malignancies in young men and, despite high cure rates with cisplatin-based multimodal therapy, a clinically relevant subset of patients develops relapsed, platinum-refractory, or treatment-resistant disease with limited salvage options and substantial long-term morbidity. This unmet need has renewed interest in immunotherapy, yet the experience in TGCT has been notably less successful than in other malignancies. Although TGCTs often display PD-L1 expression, tumor-infiltrating lymphocytes, and other features suggestive of immune en

Advances in the association between tumor immune microenvironment remodeling in osteosarcoma and the risk of pathological fractures.

Osteosarcoma (OS) is the most common primary malignant bone tumor, predominantly affecting children and adolescents, and pathological fracture (PF) represents one of its most devastating local complications, significantly worsening prognosis and quality of life. Emerging evidence demonstrates that dynamic remodeling of the tumor immune microenvironment (TIME) plays a pivotal role in both OS progression and PF occurrence. M2 polarization of tumor-associated macrophages (TAMs), enrichment of regulatory T cells (Tregs), functional exhaustion of natural killer (NK) cells, and accumulation of myelo

Integrin β1 signaling at the crossroads of cellular plasticity, the tumor microenvironment, and therapy resistance in medulloblastoma.

Medulloblastoma (MB), the most common malignant pediatric brain tumor, remains associated with relapse and long-term treatment-related toxicities. Tumor-microenvironment interactions increasingly appear to contribute to progression, stemness, and therapy resistance in brain cancers. Integrin β1, a major mediator of cell-extracellular matrix interactions, regulates survival signaling, mechanotransduction, and cancer stem cell maintenance in several tumor types, particularly glioblastoma. This mini-review discusses how developmental programs, extracellular matrix remodeling, hypoxia, and cancer

Platelets as localized conduits of TGF-β1 in the tumor microenvironment: implications for cancer progression and therapy.

Platelets are major circulating reservoirs of transforming growth factor-β1 (TGF-β1). After tumor-associated activation, they release latent TGF-β1 from α-granules or present it at the platelet surface through glycoprotein A repetitions predominant. The latent complex is then activated by integrins, proteases, mechanical forces, and local physicochemical conditions. Direct platelet-specific evidence supports roles for platelet-derived TGF-β1 in established tumor growth, epithelial-mesenchymal transition, immune suppression, and metastasis. Platelet-associated studies also suggest effects on st

Uncovering the Potential of 3D Spheroids for Modeling the Cellular Crosstalk Within the Tumor Microenvironment in HNSCC.

Head and neck squamous cell carcinoma (HNSCC) progression is profoundly influenced by dynamic cellular crosstalk within the tumor microenvironment (TME), where interactions between cancer cells, stromal components, and immune populations orchestrate therapeutic resistance, metastasis, and immune evasion. This review examines the utility of three-dimensional (3D) spheroid models as physiologically relevant platforms for investigating these cellular interactions compared with conventional two-dimensional (2D) cultures. By incorporating cancer-associated fibroblasts (CAFs), tumor-associated macro…

Pterostilbene as a pyroptosis inducer and tumor microenvironment regulator inhibits glioblastoma and enhances the efficacy of immunotherapy.

Glioblastoma (GBM) is a highly invasive tumor type associated with a high mortality rate, and the efficacy of traditional chemotherapy, targ … ro-inflammatory factors within tumor tissues, enhances the infiltration of CD8+ T cells in both the tumor microenvironment and spleen, increases the proportion of M1-type tumor-associated macrophages (TAMs), and decreases the proportion of regulatory T cells (Tregs) in the tumor microenvironment, thereby effectively reversing the immunosuppressive milieu. Further invest …

A new strategy for the treatment of advanced ovarian cancer: utilizing nanotechnology to regulate the tumor microenvironment.

Advanced ovarian cancer (AOC) is prone to recurrence, which can be attributed to drug resistance. Drug resistance may be related to the tumor microenvironment (TME), including the immune and non-immune TME. In the immune TME, the immune effector cells such as dendritic cells (DCs), M1-like tumor-associated macrophages (M1-TAMs), and T cells are inhibited. In contrast, immunosuppressive cells such as M2-like tumor-associated macrophages (M2-TAMs), myeloid-derived suppressor cells (MDSCs), and regulatory T cells (Tregs) are activated. These changes make it difficult to produce immune effects and…

Spatial transcriptomics uncovers unique tumor microenvironments in folliculotropic versus classic mycosis fungoides.

The most common subtype of cutaneous T-cell lymphoma, mycosis fungoides (MF), is characterized by proliferation of malignant T cells in the skin. In the more clinically aggressive folliculotropic MF (FMF), malignant T cells localize to follicular epithelium, whereas in classic MF, they infiltrate the dermis and epidermis. How the localization of neoplastic T cells to the follicular niche contributes to the clinical aggression in FMF is unclear. To uncover the tumor microenvironmental differences between perifollicular FMF and dermal classic MF regions, we analyzed patient samples using spatial…