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MAP4K4 regulates the immune landscape of pancreatic tumor microenvironment and provides an opportunity for immunotherapy.

Due to its widespread resistance to conventional therapy, Pancreatic Ductal Adenocarcinoma (PDAC) is expected to be the second most common cause of cancer-related death in the United States by 2030. One of the major impediments to therapeutic failure in PDAC is the presence of an immunosuppressive tumor microenvironment (TME). Here, we report the effect of MAP4K4 in regulating innate and adaptive immunity in PDAC-TME in KPC tumors. The IHC analyses revealed that the overexpression of MAP4K4 enhances tumor infiltration of macrophages and neutrophils, while decreasing the number of T cells in KP…

Nanomedicine and the tumor immune microenvironment in cancer immunotherapy: a bibliometric and knowledge-mapping analysis.

BACKGROUND: Nanomedicine can improve cancer immunotherapy by enabling tumor-selective delivery and active modulation of the tumor immune microenvironment (TIME), yet the global structure and translational trajectory of this interdisciplinary field remain unclear. METHODS: The Web of Science Core Collection and Scopus were searched from inception to February 1, 2025. After deduplication and screening, 1,110 English-language articles and reviews were included. VOSviewer, CiteSpace, Bibliometrix, and Python were used to analyze publication trends, collaboration networks, journal relationships, c

Dendritic cell-driven immune rebalancing as a systemic regulator of tumor and neurodegenerative microenvironments.

Dendritic cells (DCs) critically regulate immune dynamics within the tumor microenvironment (TME), yet the mechanisms governing the balance between effective anti-tumor immunity and immune tolerance remain incompletely defined. Existing reviews have largely examined DC biology, tumor immunology and neuroinflammation within disease-specific frameworks, leaving insufficient attention to how DC dysfunction may be compared across chronic pathological microenvironments. Here, we propose DC-driven immune rebalancing as a context-dependent framework for understanding how antigen-presenting cell state…

ZBTB10 as a potential prognosis biomarker and correlates with the tumor immune microenvironment in stomach adenocarcinoma.

BACKGROUND: ZBTB10 is a member of the zinc finger and bric-a-brac/tramtrack/broad (ZBTB) domain-containing protein family, reported to be associated with tumorigenesis and progression. However, its specific roles in oncogenesis, prognosis, and immune infiltration in stomach adenocarcinoma (STAD) remain to be elucidated. METHODS: We analyzed ZBTB10 mRNA and protein expression profiling in STAD tissues using various bioinformatics tools, including TIMER2, GEO, Human Protein Atlas (HPA) databases, and R software. Survival analysis was performed through the Kaplan-Meier plotter. UALCAN and TCGA d

Harnessing nanotechnology to modulate hypoxic tumor microenvironments: Enhanced strategies for oncological innovations.

Hypoxia, which is a characteristic of the tumor microenvironment, poses a substantial challenge to the treatment of cancer because it is the driving force behind tumor development, metastasis, and resistance to medicines. This issue arises because cancer cells grow rapidly, and the blood vessels in solid tumors are often dysfunctional, resulting in insufficient oxygen supply. This lack of oxygen makes chemotherapy and radiotherapy much less effective, as they need oxygen to work properly. Developments in nanotechnology hold the promise of introducing novel approaches to the problem of hypoxia-…

Tirabrutinib-anthracycline interactions in the brain tumor microenvironment: a focus on metabolic inactivation and resistance.

BACKGROUND: Anthracyclines (ANTs) remain essential in many anticancer regimens, yet their clinical utility is often limited by multidrug resistance. Recent studies suggest that Bruton's tyrosine kinase inhibitors (BTKis) may enhance the efficacy of ANT-based therapies, including those targeting brain tumors. This study investigates how tirabrutinib may contribute to such enhancement via interactions with aldo-keto reductase 1C3 (AKR1C3) and ABC efflux transporters. RESEARCH DESIGN AND METHODS: The inhibitory potential of tirabrutinib was evaluated using recombinant enzymes, transiently transf

The Early Effects of Esketamine on the Tumor Metastatic Microenvironment in Postoperative Lung Cancer Patients.

BACKGROUND: To investigate the early effect of esketamine on the tumor metastatic microenvironment in patients with lung cancer. METHODS: S … with lung cancer provided significant sedative and analgesic effects and affected cytokines in the tumor microenvironment.

Transforming the Tumor Microenvironment: An Outstanding AIE-Active Photosensitizer to Boost the Effectiveness of Immunotherapy.

Immunotherapy, currently the most promising therapeutic approach for cancer, has shown significant efficacy. However, its clinical effectiveness is often constrained by such factors as tumor heterogeneity, the abundance of M2 macrophages, tumor-vascular hypoxia, and the immunosuppressive microenvironment created by immune checkpoint (IC) complexes. In this work, an effective photosensitizer (TSPA) with aggregation-induced emission (AIE) nature is adopted to counter above limitations. The synthesized TSPA demonstrated potent efficacy in eradicating primary tumors because of their effective gene

Natural Anti-Inflammatory Agents in the Chemoprevention of Gliomas: Targeting Neuroinflammation and the Tumor Microenvironment.

Chronic inflammation is a well-established hallmark of cancer, playing a critical role in the initiation and progression of gliomas. Recent … a biology and highlight how these compounds may pass the blood-brain barrier (BBB) and modulate the tumor microenvironment (TME), including immune cell infiltration and cytokine profiles that may act in a pro- or anti-inflammatory manner, highlighting their capacity to inhibit GBM-associated inflammation. Each substance may differentially influence the components of the …

Chemokines and their receptors in the esophageal carcinoma tumor microenvironment: key factors for metastasis and progression.

Esophageal carcinoma (ESCA) is a highly malignant tumor with the highest incidence in Eastern Asia. Although treatment modalities for ESCA have advanced in recent years, the overall prognosis remains poor, as most patients are diagnosed at an advanced stage of the disease. There is an urgent need to promote early screening for ESCA to increase survival rates and improve patient outcomes. The development of ESCA is closely linked to the complex tumor microenvironment (TME), where chemokines and their receptors play pivotal roles. Chemokines are a class of small-molecule, secreted proteins and c…

Machine Learning Characterization of Immunometabolism in the Tumor Microenvironment and Immunotherapy Responses in Bladder Cancer.

Immune dysregulation and metabolism reprogramming are implicated in bladder cancer (BLCA), the relationships between immunometabolism (IMB) and BLCA remain poorly understood. We identified the expression patterns of IMB-related genes and their relationship with prognosis, ultimately developing a machine learning prognostic model. We performed a comprehensive investigation into UCN2 function in BLCA by qPCR, immunohistochemistry, Western blot, Transwell migration assay, and flow cytometry analysis. Two BLCA subclasses were identified, each exhibiting distinctive molecular patterns. Then, an IMB

Neutrophil-Derived Extracellular Vesicles for Facile Delivery of Diagnostic Agents to Tumor Microenvironments.

Targeted delivery of diagnostic and therapeutic agents to tumor microenvironments using nanoparticles improves the efficacy of these agents and reduces their unwarranted side effects. Numerous synthetic nanoparticle systems have been designed for this very purpose, but few have translated clinically due to poor efficacy-to-cost and efficacy-to-toxicity ratios. Biological nanoparticles such as modified extracellular vesicles (EVs) that are likely to have lower toxicities have also been developed but face challenges in clinical translation as they have primarily been produced from cancerous cell…

Desmoplastic reaction in the microenvironment of head and neck and other solid tumors: the therapeutic barrier.

Head and neck squamous cell carcinoma (HNSCC) remains a challenge due to limited prognostic biomarkers and therapeutic options. The tumor microenvironment (TME), particularly the desmoplastic reaction (DR) characterized by stromal fibrosis, plays a crucial role in cancer progression and resistance to therapy. This review aims to summarize the biological significance of DR in HNSCC initiation, progression, and treatment resistance. Histologically, DR in HNSCC correlates with invasion patterns and clinical outcomes, affecting disease-free and overall survival. The interaction between cancer-asso…

Adipocyte pyroptosis occurs in omental tumor microenvironment and is associated with chemoresistance of ovarian cancer.

BACKGROUND: Ovarian carcinoma (OC) is a fatal malignancy, with most patients experiencing recurrence and resistance to chemotherapy. In cont … ncluding OC cells, adipocytes and macrophages) coculture model was established to mimic the omental tumor microenvironment (TME) of ovarian cancer. Caspase-1 activity, ATP and free fatty acids (FFA) levels were detected by commercial kits. An adipocyte organoid model was established to assess macrophages migration and infiltration. In vitro and in vivo experiments were …

The ubiquitin-proteasome system in the tumor immune microenvironment: a key force in combination therapy.

The ubiquitin-proteasome system (UPS) plays a crucial role in modulating the proliferation, activation, and normal functioning of immune cells through the regulation of protein degradation and function. By influencing the expression of immune checkpoint-associated proteins, the UPS modulates T cell-mediated anti-tumor immune responses and can potentially facilitate the immune escape of tumor cells. Additionally, the UPS contributes to the remodeling of the tumor immunosuppressive microenvironment (TIME) by regulating B cells, dendritic cells (DCs), macrophages, and Treg cells. Targeting the UP

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… Innate and adaptive immune cells in the tumor microenvironment . Nat Immunol . ( 2013 ) 14 : 1014–22 . doi: 10.1038/ni.2703 PMC4118725 24048123 9 Pitt JM Marabelle A Eggermont A Soria JC Kroemer G Zitvogel L . … The tumor microenvironment innately modulates cancer progression . Cancer Res . ( 2019 ) 79 : 4557–66 . doi: 10.1158/0008-5472.Can-18-3962 PMC6744958 31350295 11 Wang X Zhang Y Wu Y Cheng H Wang X . …

Low muscle mass in lung cancer is associated with an inflammatory and immunosuppressive tumor microenvironment.

BACKGROUND: Computed tomographies (CT) are useful for identifying muscle loss in non-small lung cancer (NSCLC) cachectic patients. However, we lack consensus on the best cutoff point for pectoralis muscle loss. We aimed to characterize NSCLC patients based on muscularity, clinical data, and the transcriptional profile from the tumor microenvironment to build a cachexia classification model. METHODS: We used machine learning to generate a muscle loss prediction model, and the tumor's cellular and transcriptional profile was characterized in patients with low muscularity. First, we measured the…

Characterization of immune exhaustion and suppression in the tumor microenvironment of splenic marginal zone lymphoma.

The role of the tumor microenvironment (TME) and intratumoral T cells in splenic marginal zone lymphoma (sMZL) is largely unknown. In the present study, we evaluated 36 sMZL spleen specimens by single cell analysis to gain a better understanding of the TME in sMZL. Using mass cytometry (CyTOF), we observed that the TME in sMZL is distinct from that of control non-malignant reactive spleen (rSP). We found that the number of TFH cells varied greatly in sMZL, ICOS+ TFH cells were more abundant in sMZL than rSP, and TFH cells positively correlated with increased numbers of memory B cells. Treg cel…

TIGIT is Frequently Expressed in the Tumor Microenvironment of Select Lymphomas: Implications for Targeted Therapy.

Immune checkpoint inhibitors against Programmed Cell Death Protein 1/Programmed Cell (PD-1/PD-L1) and CTLA-4/B7 axes have had limited succes … s. We validated an immunohistochemical assay for TIGIT and evaluated its expression in lymphoma and tumor microenvironment (TME) cells in 661 lymphoma/leukemia biopsies. Multiplex immunofluorescence was used for correlation with normal TME cell subsets. Tumor or TME TIGIT-positivity was defined as moderate to strong membrane staining in at least 10% of tumor or TME cell …

Distinct mutational profile and immune microenvironment in microsatellite-unstable and POLE-mutated tumors.

INTRODUCTION: Mismatch repair (MMR)-deficient and DNA polymerase epsilon (POLE)-mutated tumors exhibit a high tumor mutation burden (TMB) and have been proven to be associated with good responses to immune checkpoint inhibitor treatments. However, the relationship between mutational characteristics of MMR-deficient and POLE-mutated tumors and the spatial architecture of tumor-infiltrating lymphocytes (TILs) has not been fully evaluated. METHODS: We retrieved microsatellite instability-high (MSI-high, N=20) and POLE-mutated (N=47) cases from the clinical next-generation sequencing cohort at As

Identification of a Distinct miRNA Regulatory Network in the Tumor Microenvironment of Transformed Mycosis Fungoides.

Large cell transformation of mycosis fungoides (LCT-MF) occurs in 20-50% of advanced MF and is generally associated with poor response and d … of target genes were consistent with the RNA-seq data. We further identified the immunosuppressive tumor microenvironment (TME) in LCT-MF. Moreover, our data indicated that miR-146a, -21 and -708 are associated with the immunosuppressive TME in LCT-MF. Collectively, our results suggest that the key LCT-MF associated miRs and their regulated networks may provide insight …