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Clusterin and pentraxin 3 are markers of severity during febrile neutropenia in adults with haematological malignancies receiving intensive chemotherapy.

The identification of predictive biomarkers of severity can improve patient management because febrile neutropenia can be associated with significant morbidity and mortality. We prospectively studied pentraxin 3 (PTX3), a soluble innate immunity receptor, and clusterin (CLU), a chaperone protein that binds extracellular histones during sepsis, in patients experiencing febrile neutropenia after intensive treatment for haematological malignancies. One hundred and forty-three adult patients were included, with 158 episodes of neutropenia analysed. Febrile neutropenia was observed in 119 patients

Immune Dysfunction in Uremia 2020.

Cardiovascular disease and infections are major causes for the high incidence of morbidity and mortality of patients with chronic kidney disease. Both complications are directly or indirectly associated with disturbed functions or altered apoptotic rates of polymorphonuclear leukocytes, monocytes, lymphocytes, and dendritic cells. Normal responses of immune cells can be reduced, leading to infectious diseases or pre-activated/primed, giving rise to inflammation and subsequently to cardiovascular disease. This review summarizes the impact of kidney dysfunction on the immune system. Renal failur

Reciprocal interactions between osteoclasts and nociceptive sensory neurons in bone cancer pain.

Many common cancers such as breast, prostate, and lung cancer metastasize to bones at advanced stages, producing severe pain and functional impairment. At present, the current pharmacotherapies available for bone cancer pain are insufficient to provide safe and efficacious pain relief. In this narrative review, we discuss the mechanisms used by cancer cells within the bone tumor microenvironment (TME) to drive bone cancer pain. In particular, we highlight the reciprocal interactions between tumor cells, bone-resorbing osteoclasts, and pain-sensing sensory neurons (nociceptors), which drive bon

Mixed cryoglobulinemia.

Mixed cryoglobulinemia (MC), type II and type III, refers to the presence of circulating cryoprecipitable immune complexes in the serum and manifests clinically by a classical triad of purpura, weakness and arthralgias. It is considered to be a rare disorder, but its true prevalence remains unknown. The disease is more common in Southern Europe than in Northern Europe or Northern America. The prevalence of 'essential' MC is reported as approximately 1:100,000 (with a female-to-male ratio 3:1), but this term is now used to refer to a minority of MC patients only. MC is characterized by variable

Beyond DNA Damage: Exploring the Immunomodulatory Effects of Cyclophosphamide in Multiple Myeloma.

The alkylating agent cyclophosphamide has been used in the treatment of multiple myeloma for over 60 years. At low doses, cyclophosphamide also has significant immunomodulatory activity, which can be used to modify the immunosuppressive tumor microenvironment in order to augment responses to existing therapies. Immune-mediated therapies are becoming more widespread in modern approaches to myeloma treatment. In this review, we discuss the effects cyclophosphamide has on the immune system, and how it can be used synergistically with other treatment modalities including the immunomodulatory agent

Smart Lipid-Based Nanosystems for Therapeutic Immune Induction against Cancers: Perspectives and Outlooks.

Cancer immunotherapy, a promising and widely applied mode of oncotherapy, makes use of immune stimulants and modulators to overcome the immune dysregulation present in cancer, and leverage the host's immune capacity to eliminate tumors. Although some success has been seen in this field, toxicity and weak immune induction remain challenges. Liposomal nanosystems, previously used as targeting agents, are increasingly functioning as immunotherapeutic vehicles, with potential for delivery of contents, immune induction, and synergistic drug packaging. These systems are tailorable, multifunctional,

Bridging the gap: ferroptosis of immune cells in the tumor microenvironment.

Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, is increasingly recognized as a pivotal immunomodulatory mechanism within the tumor microenvironment (TME). Beyond its well-established role in tumor cell elimination, emerging evidence reveals that immune cell subsets exhibit distinct susceptibility to ferroptosis, with profound consequences for antitumor immunity. This review systematically delineates the dual and cell-type-specific roles of ferroptosis across innate and adaptive immune populations: while ferroptosis-mediated depletion of immunosuppress

Роль ИЛ-17А в предотвращении воспламенительных реакций и прогрессии нейродегенеративных заболеваний.

IL-17A был замешан в качестве критического провоспалительного цитокина в патогенезе аутоиммунных и нейродегенеративных расстройств. Появляющиеся данные свидетельствуют о его способности активировать микроглиальные клетки и астроциты, что впоследствии приводит к созданию подстрекательских посредников, усугубляющих нейронные травмы и функциональные нарушения. Клинические наблюдения выявили продемонстрированную связь между концентрациями ИЛ-17А и дисфункцией мозгового барьера (ББД), создав патологический цикл обратной связи, усиливающий нейровоспалительные реакции. Последние достижения свидетельс

Biological response modifiers and infectious diseases: actual and potential therapeutic agents.

Biological response modifiers (BRMs) are agents which can modify the immune response to cancer or invasion of the organism by infectious agents. An explosive appearance of new BRMs has resulted from the development of recombinant gene technology and the availability of monoclonal antibodies. Colony-stimulating factors first became available for the prevention of neutropenia but may also have a role in the treatment of infections. Interleukin-1 is being tested as a modular of hematopoiesis and may be useful as a helper factor for T- and B-cell function. Immunoglobulins are being used against vi

Multiple influence of immune cells in the bone metastatic cancer microenvironment on tumors.

Bone is a common organ for solid tumor metastasis. Malignant bone tumor becomes insensitive to systemic therapy after colonization, followed by poor prognosis and high relapse rate. Immune and bone cells in situ constitute a unique immune microenvironment, which plays a crucial role in the context of bone metastasis. This review firstly focuses on lymphatic cells in bone metastatic cancer, including their function in tumor dissemination, invasion, growth and possible cytotoxicity-induced eradication. Subsequently, we examine myeloid cells, namely macrophages, myeloid-derived suppressor cells,

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… Myeloid immune cells Macrophages Macrophages are an important component of the mononuclear phagocyte system (MPS) and are key cells in the tumor immune system ( 63 ). The main immune cells that infiltrate tumors are macrophages, also known as tumor-associated macrophages (TAM) ( 64 ). … The mononuclear phagocyte system. Curr Opin Immunol. (2006) 18:49–53. doi: 10.1016/j.coi.2005.11.008. 64. Pollard JW. Tumour-educated macrophages promote tumour progression and metastasis. Nat Rev Cancer. (2004) 4:71–8. doi: 10.1038/nrc1256. 65. Wynn TA, Chawla A, Pollard JW. …

Возможная роль метаформы и фибробластного роста Factor-21 В Multical Sclerosis Neuropathology: Birds of a Feather Flock Common.

Множественный склероз (MS) — прогрессивное демиелинизирующее заболевание CNS, характеризующееся воспалением, образованием CNS-клеров и повреждением нейронной миелинской оболочки (graphical abstract). Фактор роста фибробласта 21 (FGF21) занимается различными метаболическими расстройствами и нейродегенеративными заболеваниями. FFF21 и его корецептор β-Kloth имеют существенно важное значение для процесса ремиелиции MS. Метформин, инсулин-сенсибилизирующее лекарство, которое является первой линией лечения для типа 2 Мэлитус диабета (T2DM) может оказывать потенциальное нейрозащитное воздействие, ре

The Role of TAM Receptors in Bone.

The TAM (TYRO3, MERTK, and AXL) family of receptor tyrosine kinases are pleiotropic regulators of adult tissue homeostasis maintaining organ integrity and self-renewal. Disruption of their homeostatic balance fosters pathological conditions like autoinflammatory or degenerative diseases including rheumatoid arthritis, lupus erythematodes, or liver fibrosis. Moreover, TAM receptors exhibit prominent cell-transforming properties, promoting tumor progression, metastasis, and therapy resistance in various cancer entities. Emerging evidence shows that TAM receptors are involved in bone homeostasis

Лептин и Лептин Сигналинг в множестве склерозов: обзор скрипта.

Ожирение - проблема, связанная с пандемией здоровья, - в настоящее время рассматривается как хроническое провокационное состояние, связанное со многими аутоиммунными заболеваниями, такими, как множественный склероз. Таким образом, адипокины, подстрекательские посредники, скрытые жировой тканью, играют важную роль в стимулировании иммунной реакции. В этом контексте ожирение, особенно в подростковом возрасте, как представляется, является одним из ключевых факторов развития множественного склероза. Лептин, главный провоспалительный адипокин, скрытый жировой тканью, был обнаружен у пациентов с мно

Anti-PEG Antibodies and Their Biological Impact on PEGylated Drugs: Challenges and Strategies for Optimization.

Polyethylene glycol (PEG) has been widely utilized in optimizing therapeutics due to its excellent biocompatibility and chemical stability. However, multiple dosing of PEGylated drugs may result in toxicity due to PEG accumulation in tissues, leading to the formation of anti-PEG antibodies (APAs), which can accelerate drug clearance, reduce efficacy, and alongside enhanced side effects, such as allergic reactions. Notably, pre-existing APAs have also been detected in individuals with no prior exposure to PEGylated drugs, raising additional clinical concerns. This review summarizes the mechanis

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… This modification effectively reduces renal filtration and uptake by the mononuclear phagocyte system (MPS), thus prolonging the circulation of the drug in the body. As a result, the drug is gradually released at the target tissues, ultimately enhancing therapeutic efficacy [ 8 , 9 ]. … Abbreviations The following abbreviations are used in this manuscript: PEG Polyethylene glycol APAs Anti-PEG antibodies MPS Mononuclear phagocyte system RES Reticuloendothelial system ELISA Enzyme-linked immunosorbent assay BCRs B cell receptors TFH Follicular helper T MHC Major histocompatibility complex …

Extracorporeal Photopheresis in Pediatric and Adult Patients with Graft-Versus-Host Disease.

Background/Objectives: Graft-versus-host disease (GVHD) is a severe complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) resulting from histocompatibility differences between donor and host cells leading to inflammation, tissue damage, and compromised patient outcome. Extracorporeal photopheresis (ECP) is considered as a second-line treatment administered to patients with GVHD who do not respond to corticosteroid treatment or who experience a relapse after an initial response and are therefore classified as steroid refractory (SR). The aim of this study is to evaluate

Anti-BCMA-engineered exosomes for bortezomib-targeted delivery in multiple myeloma.

AbstractExosomes have emerged as promising vehicles for delivering therapeutic cargoes to specific cells or tissues, owing to their superior biocompatibility, reduced immunogenicity, and enhanced targeting capabilities compared with conventional drug delivery systems. In this study, we developed a delivery platform using exosomes derived from monocytes, specifically designed for targeted delivery of bortezomib (Btz) to multiple myeloma (MM) cells. Our approach involved the genetic modification of monocytes to express antibodies targeting B-cell maturation antigen (anti-BCMA), because BCMA sele

Т-клеточное истощение, вызванное терапией БиТЕ в множестве миэломы: снижение инфекционного риска с помощью свободных от лечения интервалов.

Множественная миелома (ММ), которая является высокоизлечимой, но до сих пор неизлечимой гематологической халатностью, потребовала постоянного наблюдения и лечения на протяжении всей жизни пациента. Новые классы терапии, такие, как химерик антиген-рецептор (CAR) T-клеток, которые представляют собой one- вливание времени, бросило вызов постоянной системе лечения. По сравнению с ранее известной стандартной терапией T-клеточная терапия CAR, а также биконкретная терапия T-клеточной терапии (BitE) были отмечены для того, чтобы вызвать более глубокие реакции, которые, как правило, являются устойчивым

Recent Advances in CAR-Based Solid Tumor Immunotherapy.

Adoptive cell therapy using chimeric antigen receptor (CAR) technology is one of the most advanced engineering platforms for cancer immunotherapy. CAR-T cells have shown remarkable efficacy in the treatment of hematological malignancies. However, their limitations in solid tumors include an immunosuppressive tumor microenvironment (TME), insufficient tumor infiltration, toxicity, and the absence of tumor-specific antigens. Although recent advances in CAR-T cell design-such as the incorporation of co-stimulatory domains and the development of armored CAR-T cells-have shown promising results in

Hematology and Immune-Related Disorders

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… Immune-Mediated Hemolysis Immune-mediated hemolytic anemia (IMHA) occurs when an immune response is directed against antigens on erythrocytes, leading to their removal by the mononuclear phagocyte system of the spleen (extravascular hemolysis) or complement-mediated lysis (intravascular hemolysis). … Macrophages of the mononuclear phagocyte system have receptors for the Fc portion of the IgG antibody but not for IgM. Fc receptors are proteins on the surfaces of cells such as macrophages and neutrophils that contribute to the protective functions of the immune system. …

Mechanisms of Action of the New Antibodies in Use in Multiple Myeloma.

Monoclonal antibodies (mAbs) directed against antigen-specific of multiple myeloma (MM) cells have Fc-dependent immune effector mechanisms, such as complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP), but the choice of the antigen is crucial for the development of effective immuno-therapy in MM. Recently new immunotherapeutic options in MM patients have been developed against different myeloma-related antigens as drug conjugate-antibody, bispecific T-cell engagers (BiTEs) and chimeric antigen receptor (CA