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Nanoparticle Strategies for Bone Metastasis Immunotherapy: Targeting, Immune Reprogramming and Combination Therapy.

Bone metastases remain one of the most clinically devastating complications of advanced cancer, particularly in breast, prostate, and lung malignancies, where they drive pain, fractures, hypercalcemia, and progressive functional decline. Their management is further complicated by a highly immunosuppressive bone microenvironment characterized by osteoclast-driven bone destruction, myeloid cell dominance, impaired antigen presentation, and weak effector T-cell infiltration, all of which limit the activity of conventional immunotherapies. In this setting, nanoparticles are emerging not merely as

Иммуномодулирующий и противовоспалительный потенциал S-нитросглутатиона (GSNO) при множественной склерозе: обзор механизмов и терапевтических перспектив.

Многофакторная демиелинизация (МС) — это хроническое аутоиммунное заболевание центральной нервной системы (СНС), характеризующееся длительной нейроинфляминацией, окислительным стрессом, демиелинизацией и прогрессирующей нейродегенерацией. Несмотря на то, что МС остается неизлечимым, современные терапевтические средства (ТМС) помогают снизить частоту обострений и задерживать прогрессирование заболевания. Недавно разработанные инъекционные и инфузийные биологические ТМС обеспечивают целенаправленную иммуномодуляцию, но их клиническая полезность ограничена родственными методами введения и возможн

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… M1 and M2 phenotypes of macrophages and microglia also differ in their NO• profiles: M1 cells express high levels of iNOS and produce abundant NO•, supporting pathogen and tumor cell elimination, whereas M2 cells express arginase-1, which channels arginine toward ornithine and subsequently proline, a …

Immune-based cancer therapies: mechanistic insights, clinical progress, and future directions.

The field of cancer immunotherapy has evolved rapidly, offering new treatment paradigms by harnessing the body's own immune system to target and destroy malignancies. Various immunotherapeutic approaches, including immune checkpoint inhibitors, CAR-T cell therapy, cancer vaccines, cytokine therapies, and oncolytic viruses, have shown significant promise in treating different cancer types. This review provides a comprehensive examination of the historical development and recent advances in cancer immunotherapy. We discuss the mechanisms of action of key immunotherapeutic modalities, along with

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… Agents such as arginase inhibitors, glutaminase inhibitors, and lactate dehydrogenase (LDH) blockers aim to restore the metabolic fitness of effector T cells within the TME [ 242 ]. Nanotechnology is increasingly being leveraged to deliver TME-modulating agents directly to the tumor site. …

Cancer Immunotherapy in Combination with Radiotherapy and/or Chemotherapy: Mechanisms and Clinical Therapy.

Since the United States Food and Drug Administration approved the first immune checkpoint inhibitor ipilimumab for metastatic melanoma in 2011, ICIs have been approved for a range of cancers and significantly improving treatment outcomes. However, the objective response rate of ICI monotherapy remains modest (10-40%), with clinical benefit observed in only 15-20% of patients. The limited efficacy of ICIs in many patients is often attributed to poorly immunogenic ("cold") tumors. Radiotherapy and chemotherapy exhibit immunomodulatory properties that can enhance tumor immunogenicity. These effec

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… Within the TME, MDSCs produce immunosuppressive cytokines such as IL‐10 and TGF‐β, deplete T cell function through PD‐L1 upregulation, and inhibit T cell activity and antitumor immunity via arginase‐1 (ARG‐1)‐mediated arginine depletion, inducible nitric oxide synthase (iNOS), and reactive oxygen species …

Advancing CAR T-Cell Therapy in Solid Tumors: Current Landscape and Future Directions.

BackgroundChimeric Antigen Receptor (CAR) T-cell therapy has transformed the treatment of hematological malignancies, yet its application in solid tumors remains constrained by unique biological and logistical barriers.ObjectiveThis review critically examines the evolving landscape of CAR T-cell therapy in solid malignancies, with a focus on antigen heterogeneity, the immunosuppressive tumor microenvironment, and risks of on-target, off-tumor toxicity.MethodsWe outline recent advances in CAR engineering, including co-stimulatory optimization, dual- and multi-antigen targeting, armored CARs, an

Immunomodulatory Nanosystems.

Immunotherapy has emerged as an effective strategy for the prevention and treatment of a variety of diseases, including cancer, infectious diseases, inflammatory diseases, and autoimmune diseases. Immunomodulatory nanosystems can readily improve the therapeutic effects and simultaneously overcome many obstacles facing the treatment method, such as inadequate immune stimulation, off-target side effects, and bioactivity loss of immune agents during circulation. In recent years, researchers have continuously developed nanomaterials with new structures, properties, and functions. This Review provi

Immunomodulatory and antitumor effects of type I interferons and their application in cancer therapy.

During the last decades, the pleiotropic antitumor functions exerted by type I interferons (IFNs) have become universally acknowledged, especially their role in mediating interactions between the tumor and the immune system. Indeed, type I IFNs are now appreciated as a critical component of dendritic cell (DC) driven T cell responses to cancer. Here we focus on IFN-α and IFN-β, and their antitumor effects, impact on immune responses and their use as therapeutic agents. IFN-α/β share many properties, including activation of the JAK-STAT signaling pathway and induction of a variety of cellular p

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… Additionally, in tumors, Ly6C high monocytes can remain as a heterogeneous population called myeloid-derived suppressor cells (MDSC) and through up-regulation of nitric-oxide, arginase, prostaglandin-E2 and production of transforming growth factor β2 (TGF-β2) can deeply impair function of effector immune …

Абстрактный сборник ISEV2022.

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Targeting Cellular Senescence in Aging and Age-Related Diseases: Challenges, Considerations, and the Emerging Role of Senolytic and Senomorphic Therapies.

Cellular senescence is characterized by the permanent arrest of cell proliferation and is a response to endogenous and exogenous stress. The continuous accumulation of senescent cells (SnCs) in the body leads to the development of aging and age-related diseases (such as neurodegenerative diseases, cancer, metabolic diseases, cardiovascular diseases, and osteoarthritis). In the face of the growing challenge of aging and age-related diseases, several compounds have received widespread attention for their potential to target SnCs. As a result, senolytics (compounds that selectively eliminate SnCs

Circulating Tumour Cells (CTCs) in NSCLC: From Prognosis to Therapy Design.

Designing optimal (neo)adjuvant therapy is a crucial aspect of the treatment of non-small-cell lung carcinoma (NSCLC). Standard methods of chemotherapy, radiotherapy, and immunotherapy represent effective strategies for treatment. However, in some cases with high metastatic activity and high levels of circulating tumour cells (CTCs), the efficacy of standard treatment methods is insufficient and results in treatment failure and reduced patient survival. CTCs are seen not only as an isolated phenomenon but also a key inherent part of the formation of metastasis and a key factor in cancer death.

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… In MDSCs, this effect was associated with suppression of reactive oxygen species (ROS), arginase (Arg-1), and inducible nitric oxide synthase (iNOS). Lio reported that curcumin could support anticancer immunity by repressing the expression of PD-L1 in cancer cells [ 159 ]. …

Selected abstracts from the XXXVIII National Congress of the Italian Society of Hypertension (SIIA)

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CAR-T cell therapy for cancer: current challenges and future directions.

Chimeric antigen receptor T (CAR-T) cell therapies have transformed the treatment of relapsed/refractory (R/R) B-cell malignancies and multiple myeloma by redirecting activated T cells to CD19- or BCMA-expressing tumor cells. However, this approach has yet to be approved for acute myeloid leukemia (AML), the most common acute leukemia in adults and the elderly. Simultaneously, CAR-T cell therapies continue to face significant challenges in the treatment of solid tumors. The primary challenge in developing CAR-T cell therapies for AML is the absence of an ideal target antigen that is both effec

Novel therapeutic agents in clinical trials: emerging approaches in cancer therapy.

Novel therapeutic agents in clinical trials offer a paradigm shift in the approach to battling this prevalent and destructive disease, and the area of cancer therapy is on the precipice of a trans formative revolution. Despite the importance of tried-and-true cancer treatments like surgery, radiation, and chemotherapy, the disease continues to evolve and adapt, making new, more potent methods necessary. The field of cancer therapy is currently witnessing the emergence of a wide range of innovative approaches. Immunotherapy, including checkpoint inhibitors, CAR-T cell treatment, and cancer vacc

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… populations, such as tumor-associated macrophages (TAM), tumor-associated neutrophils (TAN), myeloid-derived suppressor cells (MDSC), and regulatory T cells (Tregs), which produce TGF-β, PGE2, indoleamine-2,3 dioxygenase (IDO), reactive oxygen/nitrogen species, tryptophan-2,3 dioxygenase (TDO), and arginase …

Drug repurposing in oncology: Compounds, pathways, phenotypes and computational approaches for colorectal cancer.

The strategy of using existing drugs originally developed for one disease to treat other indications has found success across medical fields. Such drug repurposing promises faster access of drugs to patients while reducing costs in the long and difficult process of drug development. However, the number of existing drugs and diseases, together with the heterogeneity of patients and diseases, notably including cancers, can make repurposing time consuming and inefficient. The key question we address is how to efficiently repurpose an existing drug to treat a given indication. As drug efficacy rem

The Fifth International Meeting of ISEV, ISEV2016, Rotterdam, The Netherlands, 4 - 7 May, 2016.

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Cancer-Associated Fibroblasts: Heterogeneity, Cancer Pathogenesis, and Therapeutic Targets.

Cancer-associated fibroblasts (CAFs) are functionally diverse stromal regulators that orchestrate tumor progression, metastasis, and therapy resistance through dynamic crosstalk within the tumor microenvironment (TME). Recent advances in single-cell multiomics and spatial transcriptomics have identified conserved CAF subtypes with distinct molecular signatures, spatial distributions, and context-dependent roles, highlighting their dual capacity to promote immunosuppression or restrain tumor growth. However, therapeutic strategies struggle to reconcile this functional duality, hindering clinica

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… In HCC, CAFs were shown to secrete CXCL12, which directly recruits CXCR4+ neutrophils that impair CD8+ T cell function via arginase‐1 (ARG1) production and reactive oxygen species (ROS)‐mediated suppression [ 6 ]. …

Моноклональные антитела: от волшебной пули до точного оружия.

Моноклональные антитела (mAbs) используются для профилактики, обнаружения и лечения широкого спектра неинфекционных и инфекционных заболеваний. За последние несколько лет рынок МП рос экспоненциально, при этом ожидаемый совокупный годовой прирост (CAGR) составил 11.07% от 2024 (В тыс.237.64 млрд. долл. США на конец 2023) к 2033 (В тыс.679.03 млрд. долл. США к концу 2033). С момента появления технологии гибридомы 1975, терапия на базе антител была реализована с использованием муринных антител, которые стали еще более гуманизированными и полностью человеческими антителами, что уменьшило риск имм

Reactive oxygen species (ROS) in cancer: from mechanism to therapeutic implications.

Reactive oxygen species (ROS) act as critical secondary messengers in various intracellular signaling pathways that regulate cellular proliferation, differentiation, and survival under normal physiological conditions. However, dysregulation of redox signaling-driven by genetic mutations, epigenetic alterations, and posttranscriptional or posttranslational modifications-plays a central role in malignant transformation and cancer progression. Cancer cells typically exhibit elevated basal ROS levels due to increased metabolic activity, mitochondrial dysfunction, and oncogene activation. This mode

Colorectal Cancer at the Crossroads: The Good, the Bad, and the Future of Platinum-Based Drugs.

Colorectal cancer (CRC) remains a significant global health challenge, ranking third in incidence and second in mortality among cancers worldwide. This review addresses the complex landscape of CRC, focusing on incidence, mortality trends, preventive strategies, and the evolving therapeutic approaches, particularly highlighting the role of platinum-based drugs like oxaliplatin (OXP). It also underscores the increasing burden of CRC, with factors such as westernized diets, aging populations, and genetic predispositions contributing to its prevalence. Therapeutically, early detection greatly enh

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… Moreover, the “Warburg effect” in proliferating tumor cells can trigger the expression of VEGF and arginase 1 (ARG1) in TAMs, resulting in macrophage recruitment and M2 polarization. …

Targeting urological cancers with CAR-T cell therapy: current landscape and future directions.

BACKGROUND: Urological cancers, including renal, bladder, and prostate cancers, are among the most prevalent solid tumors. The success of chimeric antigen receptor (CAR)-T cell therapy in hematologic malignancies has spurred its exploration for treating urological cancers. MAIN BODY: In the past decade, preclinical studies have demonstrated promising antitumor activity of CAR-T cells against urological cancers. Meanwhile, multiple clinical trials are currently underway to evaluate their safety and efficacy. However, significant challenges impede the efficacy of CAR-T cell therapy in urological

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… Key immunosuppressive cell populations, such as Tregs and MDSCs, impair T-cell function by the secretion of suppressive mediators (e.g., TGF-β, arginase-1, and nitric oxide synthase) and expressing immune checkpoint molecules; while CAFs and TAMs produce growth factors, cytokines, and matrix metalloproteinases …