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Confirmatory Trials in the Evaluation of Anticancer Medicinal Products in Man--PFS2: A Measure of Therapeutic Action-At-A-Distance.

Overall survival (OS) has emerged as the definitive regulatory "be-all, end-all" for the demonstration of benefit in cancer clinical trials. The reason and the rationale for why this is so are easily appreciated: literally a "test of time," OS is a seemingly unambiguous, agenda-free end point, independent of bias-prone variables such as the frequency and methods of assessment, clinical evaluation, and the definition of progression. However, by general consensus, OS is an imperfect end point for several reasons: First, it may often be impractical because of the length, cost, and the size of cli

Роль растворимого CD40L в аутоиммунных заболеваниях.

CD40-CD40L имеет важное значение для модуляции иммунной системы, поскольку она координирует как адаптивные, так и подстрекательские реакции. К числу аутоиммунных заболеваний относятся системная волчанка, множественный склероз, воспалительный кишечник, тромбоцитопентическая пурпура и ревматоидный артрит. Таким образом, ось CD40-CD40L является значительной терапевтической целью, несмотря на тот факт, что ее ингибирование было сначала ограничено тромбоэмболическими негативными последствиями. В результате проведенных в последнее время исследований были разработаны новые терапевтические подходы, та

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… Cross-priming involves APC presenting an exogenous antigen via MHC I to cytotoxic T lymphocyte (CTL). During cross-priming, the LT helper (LTh) and the CTL must recognise the antigen presented on the surface of the same APC. …

Дело о том, что скрытая и литичная инфекция Эпштейна-Барра была направлена на множественный склероз.

Вирус Эпштейн-Барр (EBV) тесно связан с множественным склерозом (MS). Он, вероятно, сыграет причинно-следственную роль в патогенезе MS, возможно, путем инициирования автономного иммунитета с помощью молекулярной имитации, автоантигенного представления или регулирования иммунной дистрибьюции. С другой стороны, имеющиеся данные подтверждают прямую роль ЭБВ в стимулировании деятельности по болезням MS посредством скрытых литических инфекций в циклическом режиме либо в рамках ЦНС, либо на периферии. Мы обращаем особое внимание на недавние иммунологические и вирологические выводы, подтверждающие ро

Клемастин фумарат ускоряет аккумуляцию инвалидности в прогрессивном множественном склерозе, усиливая пироптоз.

Множественный склероз (MS) — иммунопосредованное демиелинизирующее заболевание CNS. Клемастин фумарат, внезапный антигистамин и мускариновый блокатор рецепторов, обладает ремиелионирующим потенциалом в MS. Климастичная рука была добавлена в текущее клиническое исследование платформы, нацеленное на остаточную активность на основе точности, биомаркированной комбинированной терапии множественных склерозов (TRAP-MS) (Clinical Procures.gov). NCT03109288), для выявления сигнатуры ремиелинирования цереброспиновой жидкости (CSF) и для сбора данных о безопасности клемастина у пациентов независимо от ре

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, to determinate the host compartment in which IFN-β was necessary, bone marrow transplants from Ifnar1 KO mice to a WT host revealed a requirement for the hematopoietic cells, more specifically the CD11c + and CD11c - myeloid populations, that in a context lacking IFN-β lost their cross-priming …

Cancer vaccines: an update on recent achievements and prospects for cancer therapy.

Decades of basic and translational research have led to a momentum shift in dissecting the relationship between immune cells and cancer. This culminated in the emergence of breakthrough immunotherapies that paved the way for oncologists to manage certain hard-to-treat cancers. The application of high-throughput techniques of genomics, transcriptomics, and proteomics was conclusive in making and expediting the manufacturing process of cancer vaccines. Using the latest research technologies has also enabled scientists to interpret complex and multiomics data of the tumour mutanome, thus identify

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… Cross-priming for a secondary cytotoxic response to minor H antigens with H-2 congenic cells which do not cross-react in the cytotoxic assay. J Exp Med. 1976;143:1283–8. 24. Melief CJ. Cancer immunotherapy by dendritic cells. Immunity. 2008;29:372–83. 25. Schiavoni G, Mattei F, Gabriele L. … Type I interferons as stimulators of DC-mediated cross-priming: impact on anti-tumor response. Front Immunol. 2013;4:483. 26. Haabeth OA, Tveita AA, Fauskanger M, Schjesvold F, Lorvik KB, Hofgaard PO, Omholt H, Munthe LA, Dembic Z, Corthay A, Bogen B. …

Гипоксия стимулирует развитие множественного склероза, улучшая воспаление активации в макрофаге с инфекцией Porphyromonas gingivalis.

Porphyromonas gingivalis (Pg) — грамм-отрицательный анаэробный бактерий, ведущий патоген, вызывающий периодонтит. Он скрывает несколько факторов вирулентности, включая гингипатины, липополизакариды (LPS) и внешние мембранные везикли (OMVs), которые могут привести к высвобождению таких подстрекательских цитокинов, как интерлейкин (IL)-1β, альфа-фактор некроза опухоли (TNFα) и IL-6, посредством воспламенительной активации и сигнала рецептора толль-подобных (TLR). Мы продемонстрировали, что инфекция Pg в условиях гипоксики усиливает воспаление NLRP3 в макрофаге. Кроме того, мы заметили, что регул

Протокол для оценки региональной патологии оптического нерва грызунов с использованием продольных криосекций и поперечной электронной микроскопии.

Визуальная патология была установлена в качестве одной из главных особенностей демиелинизирующих заболеваний, таких, как множественный склероз (MS). Здесь мы представляем протокол для оценки региональной патологии оптического нерва грызунов с использованием продольных криосекций и поперечной электронной микроскопии. Мы описываем шаги для оптического диссекции нерва, постфиксации, обнаружения миелина, сканирования слайда основного белка миелина и анализа демиелинации. Затем мы подробно описываем процедуры пятна антителных флуоресцирующих веществ, анализ микроскопии для передачи электронов (ТЕА)

Plasmacytoid Dendritic Cells as a Novel Cell-Based Cancer Immunotherapy.

Plasmacytoid dendritic cells (pDCs) are multifaceted immune cells with a wide range of innate and adaptive immunological functions. They constitute the first line of defence against multiple viral infections and have also been reported to actively participate in antitumor immune responses. The clinical implication of the presence of pDCs in the tumor microenvironment (TME) is still ambiguous, but it is clear that pDCs possess the ability to modulate tumor-specific T cell responses and direct cytotoxic functions. Therapeutic strategies designed to exploit these qualities of pDCs to boost tumor-

Natural killer cells, macrophages and dendritic cells as innate immune therapies for blood cancers.

Innate immune cells are emerging as powerful allies in the fight against blood cancers. Natural Killer (NK) cells, macrophages, and dendritic cells (DCs)—once viewed mainly as supporting players—are now at the forefront of next-generation immunotherapies, owing to their rapid, antigen-independent tumor recognition and potent effector functions. This review highlights their distinct anti-tumor roles: NK cells’ cytotoxicity and “missing-self” recognition, the dual and adaptable nature of macrophages in the tumor microenvironment (TME), and the antigen-presenting capabilities of DCs that bridge i

Исправленный вариант: IL-12 p40 Monomer отличается от других IL-12 членов семьи на выборочно Inhibit IL-12Rβ1 Internalization and Concepting EAE.

Множественный склероз (MS) — самая распространенная болезнь человека, обезвоживающая CNS. Семья IL-12 состоит из четырех членов: IL-12 (p40:p35), IL-23 (p40:p19), p40 мономера (p40) и p40 гомодимера (p402). Поскольку все четыре члена содержат p40 в различных формах, важно использовать специальные моноклонные антитела (mAb) для характеристики этих молекул. Здесь, используя такой mAb, мы описываем выборочную потерю p40 в сыворотке пациентов с MS по сравнению со здоровым контролем. Аналогичным образом, мы также заметили сокращение p40 и увеличение IL-12, IL-23 и p402 в сыворотке мышей с экспериме

Cancer Vaccines and Beyond: The Transformative Role of Nanotechnology in Immunotherapy.

Cancer is one of the leading causes of morbidity and mortality globally, responsible for approximately 10 million deaths in 2022 and an estimated 21 million new cases in 2024. Traditional cancer treatments such as surgery, radiation therapy, and chemotherapy often present limitations in efficacy and side effects. However, immunotherapeutic vaccines have emerged as a promising approach, leveraging the body's immune system to target and eliminate cancer cells. This review examines the evolving landscape of cancer vaccines, differentiating between preventive and therapeutic strategies and highlig

Cellular immunotherapy in melanoma: the next frontier in cancer treatment.

Therapy-resistant melanoma remains a major clinical challenge despite advances with immune checkpoint inhibitors and targeted therapies, as most patients ultimately exhibit primary or acquired resistance and progress through multiple toxic treatment lines with limited durable benefit. This resistance reflects not only T-cell dysfunction but also a profound quantitative deficit of tumor-reactive lymphocytes, compounded by myeloid- and Treg-mediated immunosuppression, impaired antigen presentation, and tumor dedifferentiation programs generating a cold tumor microenvironment. Cellular immunother

Advances in improving cancer immunotherapy with nanotechnology: from smart nanoparticles to synergistic combination strategies.

Cancer immunotherapy has substantially advanced cancer treatment, achieving durable responses in select malignancies. However, its widespread application is limited by significant challenges: low efficacy in many solid tumors, severe side effects, and immune evasion facilitated by the tumor microenvironment (TME). Nanotechnology offers a promising approach to address these obstacles. By employing nanoparticles (NPs), we can precisely deliver therapeutics to tumor sites, ensure controlled release to minimize side effects, and amplify the immune response, thereby substantially boosting the effec

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… Downstream cGAS–STING activation drives IRF3 phosphorylation and nuclear translocation, resulting in robust type I interferon (IFN-α/β) production that promotes DC maturation, NK cell activation, and cross-priming of cytotoxic T lymphocytes [ 180 , 183 ]. …

Polyethyleneimine-treated polyacrylonitrile membrane hemofilter for critically ill patients receiving anticoagulant-free prolonged intermittent renal replacement therapy: a single-center, prospective, self-controlled pilot study.

BackgroundCritically ill patients requiring renal replacement therapy (RRT) are at risk of disease-related bleeding. Systemic heparinization should be avoided. AN69ST, a polyethyleneimine-treated polyacrylonitrile (AN69) membrane hemofilter, can be primed with heparin, improving its local anticoagulative activity. Prolonged intermittent RRT (PI-RRT) is of shorter duration and cheaper, considered as an alternative to continuous RRT. This study was performed to compare the success rate of anticoagulant-free PI-RRT using AN69ST versus AN69 membrane hemofilter. We also evaluated risk factors for f

Checkpoint inhibition and beyond: Precision immune engineering for the immune-privileged landscape of ocular malignancies.

Ocular malignancies, particularly uveal and conjunctival melanoma, exemplify tumors that evolve within one of the body's most immunologically constrained ecosystems, the eye's immune-privileged microenvironment. The limited success of PD-1/PD-L1 and CTLA-4 blockade in these cancers underscores the need to move beyond linear checkpoint inhibition toward multidimensional immune engineering. Through the confluence of synthetic bio-nanotechnology, AI-guided immunogenomics, and spatial immunomics, this review reframes ocular immunotherapy and redefines how tolerance and immunity might be programmat

Assessment of Psychiatric Disorders in Consultation-Liaison Setting.

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Comprehensive Single-Cell Immune Profiling Defines the Patient Multiple Myeloma Microenvironment Following Oncolytic Virus Therapy in a Phase Ib Trial.

PurposeOur preclinical studies showed that the oncolytic reovirus formulation pelareorep (PELA) has significant immunomodulatory anti-myeloma activity. We conducted an investigator-initiated clinical trial to evaluate PELA in combination with dexamethasone (Dex) and bortezomib (BZ) and define the tumor immune microenvironment (TiME) in patients with multiple myeloma treated with this regimen.Patients and methodsPatients with relapsed/refractory multiple myeloma (n = 14) were enrolled in a phase Ib clinical trial (ClinicalTrials.gov: NCT02514382) of three escalating PELA doses administered on D

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… F, Patient 10 posttreatment sample showing dendritic cell cross-priming: CD4+ (T helper cells), CD8a+ (cytotoxic T cells), and reovirus+CD163+ cells (M2 macrophages). G, Image from Patient 10 posttreatment showing apoptotic multiple myeloma cells [CD138+ and cleaved caspase-3 (CC3+)]. … PELA+ CD163 + cells were closely associated with CD4 + and CD8 + T cells indicating dendritic cell cross-priming following viral entry ( Fig. 3F ). …

Chronic stress and myeloid immunosuppression in cancer: A neuroimmune link to behavioral dysfunction.

Cancer progression is profoundly influenced by the complex interplay between the tumor microenvironment (TME), the immune system, and the patient's psychological state. This review delineates a critical pathway linking chronic stress to worsened cancer outcomes through inflammatory factors, anti-tumor immune suppression, and the induction of behavioral comorbidities. We postulate that sustained stress hormone signaling via the sympathetic nervous system and hypothalamic-pituitary-adrenal axis activation orchestrates a systemic immunosuppressive cascade. A central mechanism is the stress-induce

Future perspectives in melanoma research : Meeting report from the "Melanoma Bridge". Napoli, December 1st-4th 2015.

The sixth "Melanoma Bridge Meeting" took place in Naples, Italy, December 1st-4th, 2015. The four sessions at this meeting were focused on: (1) molecular and immune advances; (2) combination therapies; (3) news in immunotherapy; and 4) tumor microenvironment and biomarkers. Recent advances in tumor biology and immunology has led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS) of cancer patients. Immunotherapies in particular have emerged as highly successful approaches to treat patients with cancer including

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… Thus, improved cytotoxic CD8+ T cells priming and increased DC cross-priming are the major mechanisms underlying the therapeutic effect of anti-CD47 Ab, the latter requiring type I IFN pathway. …