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Targeting Chemokine Receptor CCR1 as a Potential Therapeutic Approach for Multiple Myeloma.

Multiple myeloma is an incurable plasma B-cell malignancy with 5-year survival rates approximately 10-30% lower than other hematologic cance … r cognate receptors, and is a critical component of the normal bone microenvironment as well as the tumor microenvironment of multiple myeloma. Antagonists targeting chemokine-receptor 1 (CCR1) may provide a novel approach for treating multiple myeloma. In vitro CCR1 antagonists display a high degree of specificity, and in some cases signaling bias. In vivo studies have …

Combination of STING agonist and CXCR3 antagonist disrupts immune tolerance to overcome anti-PD-L1 resistance in lung adenocarcinoma under oxidative stress.

We investigated the role of the STING1-CXCR3 axis using database data and verified it in a mouse model bearing Lewis lung carcinoma (LLC) ce … mmune checkpoint inhibitor resistance in lung adenocarcinoma by activating systemic immunity in the tumor microenvironment under oxidative stress.

Back to basic: Trials and tribulations of alkalizing agents in cancer.

UNLABELLED: "Dysregulated" metabolism is a characteristic of the cancer cell phenotype. This includes persistent use of glycolytic metabolis … ffering capacity (through, for example, oral sodium bicarbonate and TRIS) can neutralize the acidic tumor microenvironment with inhibition local invasion and proliferation which can be synergistic with the effects of chemotherapy and immunotherapy agents. Here, we describe the proton dynamics in cancer and their influence on tumor progression and metastasis. Additionall …

Rethinking the biology of metastatic melanoma: a holistic approach.

Over the past decades, melanoma-related mortality has remained nearly stable. The main reason is treatment failure of metastatic disease and the inherently linked knowledge gap regarding metastasis formation. In order to elicit invasion, melanoma cells manipulate the tumor microenvironment, gain motility, and adhere to the extracellular matrix and cancer-associated fibroblasts. Melanoma cells thereby express different cell adhesion molecules like laminins, integrins, N-cadherin, and others. Epithelial-mesenchymal transition (EMT) is physiological during embryologic development, but reactivated…

Angiogenic Properties of NK Cells in Cancer and Other Angiogenesis-Dependent Diseases.

The pathogenesis of many serious diseases, including cancer, is closely related to disturbances in the angiogenesis process. Angiogenesis is essential for the progression of tumor growth and metastasis. The tumor microenvironment (TME) has immunosuppressive properties, which contribute to tumor expansion and angiogenesis. Similarly, the uterine microenvironment (UME) exerts a tolerogenic (immunosuppressive) and proangiogenic effect on its cells, promoting implantation and development of the embryo and placenta. In the TME and UME natural killer (NK) cells, which otherwise are capable of killin…

Cancer Cell Acid Adaptation Gene Expression Response Is Correlated to Tumor-Specific Tissue Expression Profiles and Patient Survival.

The acidic pH of the tumor microenvironment plays a critical role in driving cancer development toward a more aggressive phenotype, but the underlying mechanisms are unclear. To this end, phenotypic and genotypic changes induced by adaptation of cancer cells to chronic acidosis have been studied. However, the generality of acid adaptation patterns across cell models and their correlation to the molecular phenotypes and aggressiveness of human cancers are essentially unknown. Here, we define an acid adaptation expression response shared across three cancer cell models, dominated by metabolic re…

Anticancer and Anti-Inflammatory Activities of a Standardized Dichloromethane Extract from Piper umbellatum L. Leaves.

Despite the advances in anticancer drug discovery field, the worldwide cancer incidence is remarkable, highlighting the need for new therapies focusing on both cancer cell and its microenvironment. The tumor microenvironment offers multiple targets for cancer therapy, including inflammation. Nowadays, almost 75% of the anticancer agents used in chemotherapy are derived from natural products, and plants are an important source of new promising therapies. Continuing our research on Piper umbellatum species, here we describe the anticancer (in vitro antiproliferative activity and in vivo Ehrlich …

Serum cytokines in follicular lymphoma. Correlation of TGF-β and VEGF with survival.

The prognosis of follicular lymphoma could vary with the tumor immune microenvironment. We evaluated the prognostic value of serum levels of … how the prognostic value of TGF-β and VEGF in follicular lymphoma and suggest their contribution to tumor microenvironment alterations.

GPR55 senses lactate to sustain motility in prostate cancer cells.

The enrichment of specific metabolites within the tumor microenvironment is emerging as a driver of tumor progression. Specifically, in prostate cancer (PCa), increased abundance of lactate is associated with primary-to-metastasis tumor spreading by supporting cancer cell invasiveness. Here, we highlight that the endocannabinoid receptor GPR55 is able to sense lactate and consequently trigger PCa cell amoeboid-like invasiveness, through the activation of the pro-migratory RhoA/MLC2 signaling pathway. These findings uncover a new role for GPR55 in sustaining lactate-driven PCa cell motility.

Profiling the tumor-resident microbiota in small cell lung cancer and its influence on clinical outcomes.

BACKGROUND: Increasing evidence has confirmed the existence of resident microbial communities within solid tumors and indicates that the tumor microbiota may represent a novel component of the tumor microenvironment, actively regulating cancer initiation, progression, metastasis, and therapeutic responsiveness. However, the role of tumor microbiota in small cell lung cancer (SCLC) has not been well explored. METHODS: Tumor samples were collected from 71 patients with SCLC at Shanghai Pulmonary Hospital between 2019 and 2023. A comprehensive analysis of the tumor-resident microbiota in SCLC was…

Progress and challenges in the development of advanced pancreatic cancer organoids.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with poor prognosis and rising incidence. Late detection and limited responsiveness to standard treatment translates into a 5-year overall survival of less than 12%. The pathology contributes to a desmoplastic tumor microenvironment that creates a physical barrier, leading to a dense, hypoxic environment that promotes further tumorigenesis, limited immunogenicity, and chemoresistance, resulting in a still significant translational gap in PDAC research. Feasible techniques to further elucidate tumorigenesis are indispensable be…

Beyond dose enhancement: Multi-level nanoparticle strategies to overcome biological barriers of cancer radioresistance.

Radiotherapy is a cornerstone of oncological treatment; tumor radioresistance, driven by complex factors such as enhanced DNA repair, hypoxic tumor microenvironments, and cancer stem-like cells, frequently limits clinical efficacy. Nanoparticle-based radiosensitizers represent an emerging approach to addressing these challenges. These nanoplatforms can operate through multi-level mechanisms: (1) physical enhancement via increased local energy deposition and secondary electron generation from high-Z materials such as gold and hafnium oxide; (2) chemical enhancement through localized amplificati…

Targeting the AHR-IDO1-kynurenine pathway in TREM2+ macrophages restores antitumor immunity in thyroid cancer.

INTRODUCTION: Advances in single-cell technologies have provided detailed insight into cellular heterogeneity within tumor microenvironments. However, the regulatory mechanisms driving macrophage-mediated immune suppression in thyroid cancer remain incompletely understood. METHODS: We applied integrated single-cell multi-omics approaches to tumor samples from patients and murine thyroid cancer models, including single-cell RNA sequencing, single-cell ATAC sequencing, mass cytometry, spatial/histological validation, and in vitro and in vivo functional assays. RESULTS: We identified a prominen…

Loss of TSC1/TSC2 sensitizes immune checkpoint blockade in non-small cell lung cancer.

Tuberous sclerosis complex subunit 1 (TSC1) and 2 (TSC2) are frequently mutated in non-small cell lung cancer (NSCLC), however, their effect … urvival. Collectively, TSC1/TSC2 loss defines a distinct subtype of NSCLC characterized as inflamed tumor microenvironment and superior sensitivity to ICB.

Cancer Drug Development of Carbonic Anhydrase Inhibitors beyond the Active Site.

Carbonic anhydrases (CAs) catalyze the reversible hydration of carbon dioxide to produce bicarbonate and a proton. Multiple CA isoforms are implicated in a range of diseases, including cancer. In solid tumors, continuously dividing cells create hypoxic conditions that eventually lead to an acidic microenvironment. Hypoxic tumor cells have different mechanisms in place to regulate and adjust the surrounding microenvironment for survival. These mechanisms include expression of CA isoform IX (CA IX) and XII (CA XII). These enzymes help maintain a physiological intracellular pH while simultaneousl

Molecular Mechanisms of Bone Metastasis: Which Targets Came from the Bench to the Bedside?

Bone metastases ultimately result from a complex interaction between cancer cells and bone microenvironment. However, prior to the colonization of the bone, cancer cells must succeed through a series of steps that will allow them to detach from the primary tumor, enter into circulation, recognize and adhere to specific endothelium, and overcome dormancy. We now know that as important as the metastatic cascade, tumor cells prime the secondary organ microenvironment prior to their arrival, reflecting the existence of specific metastasis-initiating cells in the primary tumor and circulating osteo

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… In this case, together with the increase in osteoclastogenesis, osteoblasts are also activated by prostate cancer cells and the tumor microenvironment leading to the accumulation of new formed bone. …

A pH-responsive iron/manganese bimetallic organic framework nanosystem for synergistic therapy of colon cancer.

A system loaded with MTO and encapsulated in SA achieved efficient drug delivery and tumor- microenvironment-triggered release. This release of MTO further exerted its chemotherapeutic effects and, in conjunction with ferroptosis, induced immunogenic cell death.

Characterization of T cell receptor repertoire in penile cancer.

Tumor-infiltrating lymphocytes (TILs) play a key role in regulating the host immune response and shaping tumor microenvironment. It has been previously shown that T cell infiltration in penile tumors was associated with clinical outcomes. However, few studies have reported the T cell receptor (TCR) repertoire in patients with penile cancer. In the present study, we evaluated the TCR repertoires in tumor and adjacent normal tissues from 22 patients with penile squamous cell carcinoma (PSCC). Analysis of the T cell receptor beta-variable (TRBV) and joining (TRBJ) genes usage and analysis of comp…

BAG3 induces α-SMA expression in human fibroblasts and its over-expression correlates with poorer survival in fibrotic cancer patients.

Hypoxia and angiogenesis in solid tumors are often strictly linked to the development of fibrotic tissues, a detrimental event that compromi … pieces of evidence revealed a pivotal role of extracellular BAG3 in pro-tumor cell signaling in the tumor microenvironment, as well as its involvement in the development of fibrosis in tumor tissues. Here we report further data showing the presence of the BAG3 receptor (Interferon-induced transmembrane protein [IFITM]-2) on the plasma membrane of normal dermal fibroblas …

Brain Tumor Vaccines: Next Steps.

High-grade gliomas remain among the most challenging malignancies despite extensive advances in molecular characterization and immunotherapy. This review highlights that while cancer vaccines consistently induce robust systemic immune responses, their clinical efficacy is limited by profound tumor heterogeneity and a highly immunosuppressive tumor microenvironment. Across peptide, dendritic cell, and mRNA-based platforms, outcomes are more strongly influenced by tumor biology than vaccine design. Emerging evidence supports a shift toward combinatorial strategies. Future progress will depend on…