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miR-96-5p-mediated Inhibition of CD47 contributes to pancreatic tumor regression via activating both innate and adaptive anti-tumor immunity.

Blocking immune checkpoints has become a viable immunotherapy option for cancer. CD47, an anti-phagocytic molecule, engages with SIRPα on macrophages to transmit a “don’t eat me” signal, facilitating immunoevasion. This research examined the molecular pathways influenced by miR-96-5p in pancreatic ductal adenocarcinoma (PDAC) and evaluates its clinical and biological significance. Utilizing bioinformatics, Western blot, luciferase reporter assays and RNA fluorescence in situ hybridization, results revealed that miR-96-5p directly targeted and inversely regulated CD47 expression, indicating pat

Establishment of Human Pituitary Neuroendocrine Tumor Derived Organoid and Its Pilot Application for Drug Screening.

CONTEXT: Precision medicine for pituitary neuroendocrine tumors (PitNETs) is limited by the lack of reliable research models. OBJECTIVE: To … servation of cellular structure, subtype-specific neuroendocrine profiles, mutational features, and tumor microenvironment heterogeneity from parental tumors was observed. A distinctive response profile in drug tests was observed among the organoids from patients with different subtypes of PitNETs. With the validation of key characteristics from parental tumors in histo …

MYC and p53 Alterations Cooperate through VEGF Signaling to Repress Cytotoxic T-cell and Immunotherapy Responses in Prostate Cancer.

UNLABELLED: Patients with castration-resistant prostate cancer (CRPC) are generally unresponsive to tumor-targeted treatments and immunother … ffector functions. Targeting VEGF-VEGFR2 signaling in vivo remodeled the immunosuppressive prostate tumor microenvironment, leading to CD8+ T-cell-mediated primary tumor and metastasis growth suppression and significantly increased overall survival in MYC- and p53-altered CRPC. VEGFR2 blockade also led to the induction of PD-L1 in tumors and produced antitumor efficacy …

Osteosarcoma tumors maintain intra-tumoral transcriptional heterogeneity during bone and lung colonization.

BACKGROUND: Tumors are complex tissues containing collections of phenotypically diverse malignant and nonmalignant cells. We know little of the mechanisms that govern heterogeneity of tumor cells nor of the role heterogeneity plays in overcoming stresses, such as adaptation to different microenvironments. Osteosarcoma is an ideal model for studying these mechanisms-it exhibits widespread inter- and intra-tumoral heterogeneity, predictable patterns of metastasis, and a lack of clear targetable driver mutations. Understanding the processes that facilitate adaptation to primary and metastatic mic

Exploring the interaction between extracellular matrix components in a 3D organoid disease model to replicate the pathophysiology of breast cancer.

In vitro models are necessary to study the pathophysiology of the disease and the development of effective, tailored treatment methods owing to the complexity and heterogeneity of breast cancer and the large population affected by it. The cellular connections and tumor microenvironments observed in vivo are often not recapitulated in conventional two-dimensional (2D) cell cultures. Therefore, developing 3D in vitro models that mimic the complex architecture and physiological circumstances of breast tumors is crucial for advancing our understanding of the illness. A 3D scaffold-free in vitro di…

Mast Cells Localize in Hypoxic Zones of Tumors and Secrete CCL-2 under Hypoxia through Activation of L-Type Calcium Channels.

Hypoxia is a condition that together with low pH, high amounts of reactive oxygen species (ROS), and increased adenosine levels characterize tumor microenvironment. Mast cells (MCs) are part of tumor microenvironment, but the effect of hypoxia on the production of MC-derived cytokines has not been fully described. Using the hypoxia marker pimonidazole in vivo, we found that MCs were largely located in the low-oxygen areas within B16-F1 mice melanoma tumors. In vitro, hypoxia promoted ROS production, a ROS-dependent increase of intracellular calcium, and the production of MCP 1 (CCL-2) in murin…

Transdifferentiations and heterogeneity in the stromal niches of uterine leiomyomas.

Uterine leiomyomas, also known as uterine fibroids (UFs), are benign smooth muscle cells tumors, the most frequent tumors in women. Even though UFs are monoclonal tumors, they contain a heterogeneous and versatile cells population. There are scarce proofs about the processes of transdifferentiation that might occur in UFs, modify the tumor microenvironment and support blood and lymph vessels formation. The stromal niches of the UFs harbor cells with angiogenic∕lymphangiogenic, as well as with vasculogenic∕lymphvasculogenic potential, which belong to a phenotypic continuum between the endotheli…

Intratumoral heterogeneity and immunotherapy resistance: clinical implications.

The impressive but incomplete clinical success of immunotherapy with immune checkpoint inhibitors makes it of paramount importance to understand and overcome immunotherapy resistance. The phenomenon of resistance to immunotherapy has been largely categorized as innate or acquired; however, many cellular and molecular mechanisms of resistance are remarkably common to both. This notion raises the possibility that resistance mechanisms develop during the coevolution of the tumor and the immune response, reflecting the multiple interactions between malignant cells and cells of the tumor immune mic

Enhancing antitumor response by combining immune checkpoint inhibitors with chemotherapy in solid tumors.

BACKGROUND: Cancer immunotherapy has changed the standard of care for a subgroup of patients with advanced disease. Immune checkpoint blocka … Combining ICB with other treatment modalities may lead to improved immunological conditions in the tumor microenvironment and could thereby enhance the antitumor immune response, even in tumor types that are so far unresponsive to ICB monotherapy. Chemotherapy, that was originally thought to be solely immunosuppressive, can exert immunomodulatory effects which may be b …

Ewing Sarcoma PDX Models.

Ewing sarcoma (EWS) is a rare malignant pediatric tumor, and patient-derived xenografts (PDXs) could represent a possibility to increase the number of available models to study this disease. Compared to cell-derived xenografts (CDX), PDXs are reported to recapitulate better tumor microenvironment, heterogeneity, genetic, and epigenetic features. They are considered reliable models due to their superior predictive value when comparing preclinical efficacy and treatment response in patients. In this chapter, we extensively describe a method for generating EWS PDX models, along with their validat…

Etiology and Pathogenesis of Gingivobuccal Cancers.

This review explores the epidemiology, molecular mechanisms, and immune interactions underlying gingivobuccal squamous cell carcinoma, a distinct oral cancer subtype strongly associated with tobacco and areca nut use. It highlights key genetic mutations, epigenetic alterations, and tumor microenvironment factors that drive carcinogenesis and influence prognosis. The role of oral potentially malignant disorders in early detection is emphasized, along with the importance of molecular subtyping for risk stratification. Advances in understanding tumor biology provide promising opportunities for de…

IL-6 in the Ecosystem of Head and Neck Cancer: Possible Therapeutic Perspectives.

Interleukin-6 (IL-6) is a highly potent cytokine involved in multiple biological processes. It was previously reported to play a distinct role in inflammation, autoimmune and psychiatric disorders, ageing and various types of cancer. Furthermore, it is understood that IL-6 and its signaling pathways are substantial players in orchestrating the cancer microenvironment. Thus, they appear to be potential targets in anti-tumor therapy. The aim of this article is to elucidate the role of IL-6 in the tumor ecosystem and to review the possible therapeutic approaches in head and neck cancer.

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… It requires a broader view, and one must take the whole tumor microenvironment into account, as was also proposed for HNSCC in our previous review [ 13 ]. … Tumor Microenvironment: The Role of the Tumor Stroma in Cancer J. Cell. Biochem. 2007 101 805 815 10.1002/jcb.21159 17226777 12. Lorusso G. Rüegg C. The Tumor Microenvironment and Its Contribution to Tumor Evolution toward Metastasis Histochem. …

Translational Models for Glioblastoma: Revolutionizing Drug Development and Personalized Medicine through Clinical Insights.

Glioblastoma (GBM) remains one of the most aggressive and treatment resistant brain tumors and continues to present major challenges for effective therapeutic development. The failure of numerous late-stage clinical trials highlights the limited predictive value of conventional preclinical models. Although established cell lines, two-dimensional cultures, and animal models have been extensively employed, existing platforms fail to adequately recapitulate the complex tumor microenvironment, blood brain barrier function, and interpatient heterogeneity that drive therapeutic resistance in GBM. To…

PD-1 inhibitor combined with chemoradiotherapy in two cases of ovarian cancer brain metastases: a case report.

BACKGROUND: To investigate the clinical efficacy and potential mechanisms of immune checkpoint inhibitors (PD-1 inhibitors) combined with chemotherapy and targeted therapy in ovarian cancer patients with brain metastases, and to analyze the relationship between the number of brain metastases, tumor microenvironment characteristics, and prognosis. MATERIALS AND METHODS: A retrospective analysis was conducted on the clinical data of two ovarian cancer patients with brain metastases. One patient had a single brain metastasis and received comprehensive treatment including surgery, radiotherapy, c…

Polydopamine-coated hollow mesoporous silica nanoparticles loaded with lupeol regulates immune microenvironment in gastric cancer mice by down-regulating IL-10 through regulating NF-κb signaling.

BACKGROUND: Modulating the immune microenvironment is a promising strategy against gastric cancer. OBJECTIVES: This study explored the mechanism of polydopamine-coated hollow mesoporous silica nanoparticles loaded with lupeol (Lupeol-PDA-HMSNs) in regulating the immune microenvironment via the NF-κB/IL-10 axis. METHODS: Lupeol-PDA-HMSNs were synthesized and characterized. A gastric cancer mouse model was established and mice were randomly assigned to control, free Lupeol, PDA-HMSNs, or Lupeol-PDA-HMSNs groups. Tumor growth was monitored. Immune cell profiles and serum cytokines were assessed

Multi-omics and spatial transcriptomics reveal that S100A10 drives CD8+ T-cell exhaustion and immune evasion in hepatocellular carcinoma through cPLA2-5-LOX-mediated arachidonic acid metabolism and ferroptosis.

Immune evasion in hepatocellular carcinoma (HCC) represents a major biological barrier limiting the efficacy of immunotherapy, yet its molecular basis remains incompletely understood. Increasing evidence indicates that tumor metabolic reprogramming and ferroptosis-related signaling play critical roles in shaping an immunosuppressive tumor microenvironment (TME); however, the specific regulatory factors involved remain unclear. This study aims to systematically elucidate the functional role of S100 calcium-binding protein A10 (S100A10) in immune evasion in HCC, with a particular focus on the mo…

Deciphering the immune landscape of parathyroid carcinoma: implications for immunotherapeutic responsiveness.

BACKGROUND: Parathyroid carcinoma is a rare endocrine malignancy with limited therapeutic options. Immune checkpoint blockade targeting the PD-1/PD-L1 axis has transformed the management of several solid tumors; however, its role in parathyroid carcinoma remains largely unexplored. Given that the response to immunotherapy is influenced not only by PD-L1 expression but also by the tumor immune microenvironment (TIME), characterization of the immune landscape in parathyroid carcinoma may provide insights into its potential therapeutic vulnerability. OBJECTIVE: To evaluate PD-L1 expression and c

C-C chemokine receptor 4 is a candidate for regulatory T-cell-depletion immunotherapy in differentiated thyroid cancer.

OBJECTIVE: Immunotherapy using immune checkpoint inhibitors is a standard treatment option for many types of malignancies but is not effective for differentiated thyroid cancer (DTC). Regulatory T-cells (Tregs), which are one of the main suppressive factors in the tumor microenvironment, are another important target for immunotherapy. This study investigated the characteristics of Tregs in DTC with the aim of further developing immunotherapy. METHODS: Peripheral blood lymphocytes (PBLs) and tumor-infiltrating lymphocytes (TILs) were obtained from 12 patients with DTC and 12 patients with goit…

Single-cell RNA sequencing reveals that MYBL2 in malignant epithelial cells is involved in the development and progression of ovarian cancer.

BACKGROUND: Ovarian carcinoma (OC) is a prevalent gynecological malignancy associated with high recurrence rates and mortality, often diagnosed at advanced stages. Despite advances in immunotherapy, immune exhaustion remains a significant challenge in achieving optimal tumor control. However, the exploration of intratumoral heterogeneity of malignant epithelial cells and the ovarian cancer tumor microenvironment is still limited, hindering our comprehensive understanding of the disease. MATERIALS AND METHODS: Utilizing single-cell RNA sequencing (scRNA-seq), we comprehensively investigated th…

Predictive Value of Circulating Tumor Cells in Neoadjuvant Chemoimmunotherapy for Non-Small Cell Lung Cancer.

BACKGROUND: The incorporation of immune checkpoint blockade into preoperative regimens has significantly advanced the clinical management of locally advanced non-small cell lung cancer (NSCLC). Standard imaging modalities frequently fall short in assessing actual pathological regression. Our research sought to evaluate circulating tumor cells (CTCs) as an adjunct predictive tool, while uncovering the transcriptomic shifts within the tumor microenvironment that facilitate cellular shedding. METHODS: A prospective cohort of 39 patients with NSCLC received neoadjuvant programmed cell death prote…