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Repurposing tumor-derived extracellular vesicles with an adhesive carboxymethyl chitosan-based hydrogel for spinal cord injury repair.

Spinal cord injury (SCI) triggers a cascade of pathological events, including persistent neuroinflammation and glial scar formation, which severely hinder axonal regeneration and motor functional recovery. Inspired by the immunosuppressive and regenerative features of the tumor microenvironment, this study introduces a high-reward strategy that repurposes tumor-derived extracellular vesicles (TDEVs) for SCI repair. To ensure localized delivery and enhance safety, TDEVs are incorporated into an injectable adhesive hydrogel composed of carboxymethyl chitosan (CMC) and polydopamine (PDA), crossli…

Pseudomonas aeruginosa Exacerbates Bladder Cancer Progression by Activating Cancer-Driven Immunosuppression.

Pseudomonas aeruginosa infection is still a serious problem among immunocompromised patients who have advanced urinary tract malignancies, yet the impact of P. aeruginosa on disease progression remains poorly defined. In this study, we show that urinary tract infections caused by P. aeruginosa exacerbated bladder cancer progression in murine models, primarily by inducing an immunosuppressive tumor microenvironment. Mechanistically, P. aeruginosa activated Toll-like receptor 5 (TLR5) on bladder cancer cells, triggering phosphorylation of ERK1/2 and subsequent secretion of the chemokine CCL20. T…

The PLAU-ITGB1-TGF-β axis orchestrates spatiotemporal reprogramming of fibroblasts at the invasive front to drive dual immunosuppressive niche and immunotherapy resistance in oral squamous cell carcinoma.

The initiation and progression of cancer are driven by the dynamic interplay between somatic mutations and the tumor microenvironment. Identifying core cell populations driving malignant transformation and understanding the intercellular interactions within the tumor microenvironment are, therefore, crucial for early diagnosis and effective treatment. Here, we construct a spatiotemporal atlas of oral squamous cell carcinoma (OSCC) progression by integrating multi-omics approaches. Our analysis reveals that the critical driver gene PLAU activates the TGF-β pathway via ITGB1, thereby promoting t…

Навигация терапевтического ландшафта миеломы: иммунотерапия, микроокружающая среда и сопротивление.

Иммунотерапии, включая клетки химерика антигенного рецептора (CAR) T, биконкретные Т-клеточные агенты (BITEs) и антитело-наркотики (ADC), изменили ландшафт лечения множественной миеломы (MM). Несмотря на высокие показатели первоначальных ответов, достижение долговременной ремиссии по-прежнему сопряжено с трудностями из-за частых рецидивов, вызванных комплексными механизмами терапевтического сопротивления. В этом обзоре мы всесторонне исследуем врожденную устойчивость к опухоли, такую, как врожденный и приобретенный антигенный выход, обусловленный геномными изменениями, структурными вариациями

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… Concurrently, overcoming extrinsic resistance mechanisms by the tumor microenvironment is equally important and urgent. … The role of tumor microenvironment in multiple myeloma development and progression. Cancers. 2021;13:217. doi: 10.3390/cancers13020217. 133. Mitsiades C.S., Mitsiades N.S., Munshi N.C., Richardson P.G., Anderson K.C. …

An alginate-based biomimetic nanozyme metabolic immunomodulator for sensitizing photothermal-immunotherapy in postoperative breast cancer.

The postoperative therapy for breast cancer is significantly restricted by local immunosuppression and the non-healing of infected wounds. We developed a botanical/nanozyme/polysaccharide metabolic immunomodulator (BCZG), using alginate as the primary scaffold, integrating baicalein-loaded carbon nanozyme into a polydopamine-modified alginate hydrogel. In the acidic tumor microenvironment, the BCZG mimicked NOX, OXD, and GSHOx activities, which could deplete NADH/ATP and glutathione to block heat shock protein synthesis and amplify ROS storms for achieving robust immunogenic cell death. Meanwh…

Non-coding RNAs in gastric cancer immunotherapy: mechanisms and clinical implications.

Gastric cancer immunotherapy, recognized as the fourth primary treatment modality after surgery, radiotherapy, and chemotherapy, encompasses strategies such as immune checkpoint inhibitors and cellular immunotherapy and provides new avenues for cancer control. Recent studies have revealed that non-coding RNAs (ncRNAs), including miRNAs, lncRNAs, piRNAs, siRNAs, and circRNAs, drive the progression of gastric cancer primarily through three regulatory axes: epigenetic modification, transcriptional reprogramming, and tumor microenvironment remodeling. These processes are closely linked to tumor im…

The Mechanism and Latest Progress of m6A Methylation in the Progression of Pancreatic Cancer.

Pancreatic cancer (PC), known as the "king of cancers," is characterized by an exceptionally low five-year survival rate, posing a formidabl … of m6A's role in PC by delineating its involvement in four key areas of tumorigenesis: the hypoxic tumor microenvironment, metabolic reprogramming, immune microenvironment, and resistance mechanisms. Additionally, the review addresses the emerging frontier of m6A interactions with non-coding RNAs (ncRNAs), offering insights into the potential therapeutic and prognostic …

Mycosis fungoides and IL-4/13 inhibitors: what is known and unmet needs.

INTRODUCTION: Dupilumab is a monoclonal antibody that inhibits the IL-4 receptor alpha, preventing the binding of IL-4 and IL-13 and the subsequent signal transduction. Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common form of cutaneous T-cell lymphoma (CTCL). Several cases of MF have been reported following the initiation of dupilumab in patients previously diagnosed with atopic dermatitis. AREAS COVERED: This article is a narrative review of the current state of knowledge regarding the correlation between dupilumab and the development of CTCL. Clinical studies on this topi

Three-Dimensional Models: Biomimetic Tools That Recapitulate Breast Tissue Architecture and Microenvironment to Study Ductal Carcinoma In Situ Transition to Invasive Ductal Breast Cancer.

Diagnosis of ductal carcinoma in situ (DCIS) presents a challenge as we cannot yet distinguish between those lesions that remain dormant fro … outline the significance of 3D culture models as reliable pre-clinical tools that mimic the in vivo tumor microenvironment and facilitate the study of DCIS lesions as they progress to invasive breast cancer. We also discuss the role of CAFs and other stromal cells in DCIS transition as well as the clinical significance of emerging technologies like tumor-on-chip and co- …

The β-glucan nanotube carrier achieves detoxification and efficacy enhancement of celastrol in intrahepatic cholangiocarcinoma therapy by increasing targeted controlled release and macrophage polarization.

Celastrol (Cel) is a monomer from a famous traditional Chinese medicine named Tripterygium wilfordii Hook. f. Cel has shown great potential in treating intrahepatic cholangiocarcinoma (ICC) but still faces problems, including poor water solubility, high toxicity, and lack of targeting ability. Thus, the present work constructed a drug-delivery system using black fungus polysaccharide self-assembled -nanotubes (BFP). Cel-loaded nanotubes (BFP-Cel) were confirmed to have a high loading content of Cel (38 %), liver targeting, and enzyme-controlled release abilities. Moreover, BFP carriers could s

New insights into non-small cell lung cancer bone metastasis: mechanisms and therapies.

Bone metastasis is a common cause of death in patients with non-small cell lung cancer (NSCLC), with approximately 30-40% of NSCLC patients eventually developing bone metastases. Bone metastasis, especially the occurrence of skeletal-related events (SREs), significantly reduces overall survival (OS) and quality of life (QoL) in patients. Although bone-targeting agents (BTAs) have been shown to reduce SREs and improve QoL in NSCLC patients with bone metastases, the prognosis for these patients remains poor. Understanding the underlying molecular pathways of bone metastasis is crucial for the de

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… Hypoxia-inducible factor-1α (HIF-1α), produced in the hypoxic tumor microenvironment (TME), is closely associated with tumor metastasis. A retrospective analysis indicates that HIF-1α is highly expressed in NSCLC and can be considered a predictive factor of bone spread and poor prognosis 23 . … microenvironment bone marrow-derived mesenchymal stem cells matrix metalloproteinases extracellular matrix bone sialoprotein circulating tumor cells programmed cell death 1 ligand 1 C-X-C motif chemokine ligand 12 C-X-C receptor soluble vascular cell adhesion molecule-1 intercellular adhesion …

B-cell intrinsic RANK signaling cooperates with TCL1 to induce lineage-dependent B-cell transformation.

B-cell malignancies, such as chronic lymphocytic leukemia (CLL) and multiple myeloma (MM), remain incurable, with MM particularly prone to relapse. Our study introduces a novel mouse model with active RANK signaling and the TCL1 oncogene, displaying both CLL and MM phenotypes. In younger mice, TCL1 and RANK expression expands CLL-like B1-lymphocytes, while MM originates from B2-cells, becoming predominant in later stages and leading to severe disease progression and mortality. The induced MM mimics human disease, exhibiting features like clonal plasma cell expansion, paraproteinemia, anemia, a

Lymphatic vasculature in ovarian cancer.

Ovarian cancer (OVCA) is the second most common gynecological cancer and one of the leading causes of cancer related mortality among women. … ic architecture of the ovary, we discuss the role of lymphatic circulation in regulation of ovarian tumor microenvironment, metabolic basis of the upregulation of lymphangiogenesis which is often observed during progression of ovarian metastasis and ascites development. Further we describe the implication of several mediators which influence both lymphatic vasculature a …

A robust control system for targeting melanoma by a supermolecular DDMC/paclitaxel complex.

A DEAE-dextran-MMA copolymer (DDMC)-paclitaxel (PTX) conjugate was prepared using PTX as the guest and DDMC as the host. The resistance of B16F10 melanoma cells to PTX was confirmed, while the DDMC-PTX conjugate showed excellent anticancer activity that followed the Hill equation. The robustness in the tumor microenvironment of the allosteric system was confirmed via BIBO stability. This feedback control system, explained via a transfer function, was very stable and showed the sustainability of the system via a loop, and it showed superior anti-cancer activity without drug resistance from canc…

The role of TGF-β in bone metastasis: novel therapeutic perspectives.

The skeleton is a preferred site for cancer metastasis. These bone metastases cause dysregulated bone remodeling and the associated morbidity of fractures, pain, hypercalcemia and catastrophic nerve compression syndromes. Transforming growth factor-β (TGF-β) is stored in mineralized bone matrix, and released and activated by osteoclastic bone resorption. Once activated, TGF-β stimulates nearby metastatic tumor cells within the bone microenvironment to secrete factors that further drive osteolytic destruction of the bone. Therefore, TGF-β and its signaling constitute a critical component drivin

Dual inhibition of ERα/NF-κB pathways coupled with sonodynamic therapy via a multifunctional AIEgen.

Here we report TBEP, a trifunctional sonosensitizer integrating aggregation-induced emission characteristics for ultrasound-triggered reactive oxygen species generation, estradiol-mediated ERα targeting, and pterostilbene-derived inflamation inhibition. This modular platform synergizes spatially precise SDT with tumor microenvironment modulation, offering a promising strategy for breast cancer therapy.

Advances and challenges in experimental models for Epstein-Barr virus research.

Epstein-Barr virus (EBV), the first identified human oncovirus, is a ubiquitous γ-herpesvirus etiologically linked to diverse malignancies, … LI) cultures, spheroids, and patient-derived organoids (PDOs), better mimic tissue architecture and tumor microenvironments and yet face challenges in scalability, dynamic microenvironments, and immune component integration. Animal models, such as humanized mice, rabbits, and tree shrews, have been developed that overcome in vitro limitations by recapitulating systemic …

AMPK is necessary for Treg functional adaptation to microenvironmental stress during malignancy and viral pneumonia.

CD4+FOXP3+ Treg cells maintain self tolerance, suppress the immune response to cancer, and protect against tissue injury during acute inflam … thyltransferase 1 to promote transcriptional programs associated with mitochondrial function in the tumor microenvironment. During viral pneumonia, we found that AMPK sustains metabolic homeostasis and mitochondrial activity. Induction of DNA hypomethylation was sufficient to rescue mitochondrial mass in AMPK-deficient Treg cells, linking AMPK function to mitochondrial …

VISTA neutralization by immunization reprograms immunosuppression and augments vaccine efficacy in renal carcinoma.

BACKGROUND: Renal carcinoma remains a highly lethal malignancy, and tumor vaccine efficacy is frequently hampered by a profoundly immunosuppressive tumor microenvironment. V-domain Ig suppressor of T-cell activation (VISTA), an inhibitory immune checkpoint enriched in myeloid cells and regulatory T cells (Tregs), represents a critical barrier to effective antitumor immunity. Targeting VISTA may therefore provide a promising strategy to overcome immune suppression and enhance tumor vaccine efficacy. METHODS: Recombinant adenoviral vaccines encoding carbonic anhydrase IX (CAIX) and VISTA (Ad-CA…

The role of immunological markers in the diagnosis of colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) remains one of the most common solid malignancies in the Western population. Despite advances in screening, diagnostics, and treatment, there are still no highly specific tests for early diagnosis or biomarkers that can reliably identify high-risk patients or monitor disease progression more effectively than currently established tumor markers. The pathogenesis of CRC is closely associated with chronic inflammation, oxidative stress, and remodeling of the tumor microenvironment. The present study focuses on several biomarkers selected based on available li…