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Мак-1 регулирует иммуноусилительное подавление конкретной стадии болезни через нитриковый путь в аутоиммунном заболевании.

Интегрин Мак-1 играет важнейшую роль в развитии множественного склероза (MS); однако лежащий в его основе механизм не в полной мере изучен. Здесь мы разработали мышь с миелоидной мышью Мак-1-дефицит. Используя экспериментальную аутоиммунную энцефаломиэлит (EAE) модель мыши MS, мы сообщаем, что Мак-1 на миелиоидных клетках является ключом к развитию болезней. Наши данные показывают, что миелиоидный Мак-1 значительно повышает интенсивность EAE и затрудняет регрессию заболеваний. Потеря Mac-1 увеличивает количество клеток Gr-1+ в периферийных тканях и CNS и предпочтительно ускоряет переход моноци

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… These frozen sections were analyzed by immunofluorescent staining for leukocyte infiltration (CD45), myelination (FluoroMyelin and myelin basic protein), microglia (TMEM119) and their activation [major histocompatibility complex class II (MHCII)], fibrin(ogen) deposition (Fg), neurofilaments (SMI-312 …

Targeting cancer stem cells with CAR-based immunotherapy: biology, evidence, and future directions.

Cancer stem cells (CSCs) are pivotal in tumor initiation, progression, and relapse, underscoring the need for targeted therapies to achieve lasting responses. This review delves into CSC biology, highlighting their tumor-initiating potential demonstrated through limiting dilution assays and their role in resistance to therapies. Although successful CAR therapies, such as anti-CD19 CAR T-cells, can induce complete responses without directly targeting CSCs, CAR strategies focusing on CSCs may offer promising avenues to prevent recurrence. We assess CAR therapies targeting CSC-specific antigens,

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… The CAR T-cells can eliminate tumor cells without needing major histocompatibility complex-I (MHC-I) presentation, making them highly suitable for targeting CSCs that may downregulate MHC-I expression [ 15 ]. …

Successful salvage of a severe COVID-19 patient previously with lung cancer and radiation pneumonitis by mesenchymal stem cells: a case report and literature review.

During the COVID-19 pandemic, elderly patients with underlying condition, such as tumors, had poor prognoses after progressing to severe pneumonia and often had poor response to standard treatment. Mesenchymal stem cells (MSCs) may be a promising treatment for patients with severe pneumonia, but MSCs are rarely used for patients with carcinoma. Here, we reported a 67-year-old female patient with lung adenocarcinoma who underwent osimertinib and radiotherapy and suffered from radiation pneumonitis. Unfortunately, she contracted COVID-19 and that rapidly progressed to severe pneumonia. She respo

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… SARS-CoV-2 promotes the expression of major histocompatibility complex (MHC) molecules and co-stimulatory receptors of DCs that represent its maturation. …

Novel Therapies to Address Unmet Needs in ITP.

Primary immune thrombocytopenia (ITP) is an autoimmune disorder that causes low platelet counts and subsequent bleeding risk. Although current corticosteroid-based ITP therapies are able to improve platelet counts, up to 70% of subjects with an ITP diagnosis do not achieve a sustained clinical response in the absence of treatment, thus requiring a second-line therapy option as well as additional care to prevent bleeding. Less than 40% of patients treated with thrombopoietin analogs, 60% of those treated with splenectomy, and 20% or fewer of those treated with rituximab or fostamatinib reach su

Tumour-associated macrophages: versatile players in the tumour microenvironment.

Tumour-Associated Macrophages (TAMs) are one of the pivotal components of the tumour microenvironment. Their roles in the cancer immunity are complicated, both pro-tumour and anti-cancer activities are reported, including not only angiogenesis, extracellular matrix remodeling, immunosuppression, drug resistance but also phagocytosis and tumour regression. Interestingly, TAMs are highly dynamic and versatile in solid tumours. They show anti-cancer or pro-tumour activities, and interplay between the tumour microenvironment and cancer stem cells and under specific conditions. In addition to the c

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… Macrophages also process and present antigens to T cells via major histocompatibility complex (MHC) molecules aiding adaptive immune response ( Mascarau et al., 2023 ; van Elsas et al., 2023 ). Interestingly, tissue-specific macrophages display unique functions. … Distinct responsiveness of tumor-associated macrophages to immunotherapy of tumors with different mechanisms of major histocompatibility complex class I downregulation. Cancers (Basel) 13 (12), 3057. 10.3390/cancers13123057 Pu Y., Ji Q. (2022). …

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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… This LNP-based multiplex editing strategy addresses a key limitation of current allogeneic CAR-T manufacturing by enabling simultaneous disruption of TCR signaling, major histocompatibility complex (MHC) class I expression, and inhibitory checkpoint pathways in a single non-viral delivery step. …

Facing challenges with hope: universal immune cells for hematologic malignancies.

Many patients have achieved a favorable overall survival rate since allogenic hematopoietic stem cell transplantation (allo-HSCT) has been widely implemented to treat hematologic malignancies. However, graft-versus-host disease (GVHD) and complications of immunosuppressive drugs after allo-HSCT are the main causes of non-relapse mortality and a poor quality of life. In addition, GVHD and infusion-induced toxicity still occur with donor lymphocyte infusions (DLIs) and chimeric antigen receptor (CAR) T-cell therapy. Because of the special immune tolerance characteristics and anti-tumor ability o

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… All universal immune cells are stimulated in a major histocompatibility complex (MHC)-independent manner. When universal immune cells are exposed to tumor cells, universal immune cells become activated for tumor rejection and do not target normal cells regardless of derivation. …

Облученные CD19 химерик антигенные рецепторы YTS клетки сохраняют антитуматорную активность и предлагают масштабируемую альтернативу аутологической терапии CAR-T.

Химерическая антигенная рецепторная (CAR) терапия клеток революционизировала лечение таких гематологов, как лимфома и множественная миелома. Однако их успех ограничивается высокими производственными издержками, зависимостью от аутологических Т клеток, переменным качеством продукта и такими опасными для жизни токсичными свойствами, как синдром выброса цитокина. В отличие от этого клетки естественного убийцы (НК) предлагают более безопасную, более гибкую альтернативу, однако их клинический перевод по-прежнему сдерживается сложными протоколами расширения и высокими производственными издержками. З

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… NK cells offer several advantages over T cells for immunotherapy, including reduced adverse effects such as cytokine release syndrome and immune-effector cell-associated neurotoxicity.6 Unlike T cells, NK cells are not restricted by major histocompatibility complex (MHC) compatibility, allowing their …

Cancer treatment using peptides: current therapies and future prospects.

This paper discusses the role of peptides in cancer therapy with special emphasis on peptide drugs which are already approved and those in clinical trials. The potential of peptides in cancer treatment is evident from a variety of different strategies that are available to address the progression of tumor growth and propagation of the disease. Use of peptides that can directly target cancer cells without affecting normal cells (targeted therapy) is evolving as an alternate strategy to conventional chemotherapy. Peptide can be utilized directly as a cytotoxic agent through various mechanisms or

Exploring the impact of m6A modification on immune diseases: mechanisms and therapeutic implication.

N6-methyladenosine (m6A) is a chemical modification of RNA and has become a widely discussed topic among scientific researchers in recent years. It is distributed in various organisms, including eukaryotes and bacteria. It has been found that m6A is composed of writers, erasers and readers and is involved in biological functions such as splicing, transport and translation of RNA. The balance of the human immune microenvironment is important for human health abnormalities. Increasing studies have found that m6A affects the development of immune diseases such as inflammatory enteritis and system

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… In another study, reduced release of major histocompatibility complex II (MHCII), costimulatory molecules (CD80, CD86), and cytokines [interferons-γ (IFN-γ), IL-12] was observed, along with a decreased ability to mediate T-cell activation in DCs that were knocked down for METTL3, exhibiting immature …

Targeted Alpha Therapy: Progress in Radionuclide Production, Radiochemistry, and Applications.

This review outlines the accomplishments and potential developments of targeted alpha (α) particle therapy (TAT). It discusses the therapeutic advantages of the short and highly ionizing path of α-particle emissions; the ability of TAT to complement and provide superior efficacy over existing forms of radiotherapy; the physical decay properties and radiochemistry of common α-emitters, including 225Ac, 213Bi, 224Ra, 212Pb, 227Th, 223Ra, 211At, and 149Tb; the production techniques and proper handling of α-emitters in a radiopharmacy; recent preclinical developments; ongoing and completed clinica

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… Targeted cancer cell ablation in mice by an α-particle-emitting astatine-211-labeled antibody against major histocompatibility complex class I chain-related protein A and B Biochem. Biophys. Res. Commun. 2018 506 1078 1084 10.1016/j.bbrc.2018.10.157 30409432 108. Beyer G.-J. Miederer M. …

Sclerosing diseases of the skin.

Sclerosing skin diseases comprise a group of distinct dermatological conditions characterized by fibrotic changes that may severely impair patients' quality of life. These conditions often present with cutaneous manifestations and, in some cases, may extend to extracutaneous tissues, potentially resulting in significant morbidity and mortality. This review explores the current understanding of the four most prevalent sclerosing skin diseases - localized scleroderma (morphea), systemic sclerosis (SSc), scleromyxedema, and scleredema adultorum of Buschke - as well as sclerotic conditions induced

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… Major histocompatibility complex class I and class II alleles may confer susceptibility to or protection against morphea: findings from the Morphea in Adults and Children cohort [published correction appears in Arthritis Rheumatol. 2015 Mar;67(3):751. …

Полигенная природа множественного склероза: генетические варианты, иммунологические модуляции и экологические связи.

Множественный склероз (MS) — изнуряющее воспалительное расстройство центральной нервной системы, характеризующееся обезвоживанием, — в значительной степени зависит от полигенных вариаций. Хотя конкретная причина НР остается неясной, считается, что она возникает в результате сложного взаимодействия генетических и экологических факторов. Последние исследования были сосредоточены на полигенном характере генетических изменений, связанных с риском НР. В настоящем обзоре подчеркивается важнейшая роль этих генетических вариантов в формировании восприимчивости к болезням и их развития. Специфические а

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… The HLA region, the Major Histocompatibility Complex (MHC), is located on chromosome 6p21 and spans a genomic area of 7.6 megabases. …

Prevention of CMV/EBV reactivation by double-specific T cells in patients after allogeneic stem cell transplantation: results from the randomized phase I/IIa MULTIVIR-01 study.

INTRODUCTION: Allogeneic stem cell transplantation is used to cure hematologic malignancies or deficiencies of the hematopoietic system. It is associated with severe immunodeficiency of the host early after transplant and therefore early reactivation of latent herpesviruses such as CMV and EBV within the first 100 days are frequent. Small studies and case series indicated that application of herpes virus specific T cells can control and prevent disease in this patient population. METHODS: We report the results of a randomized controlled multi centre phase I/IIa study (MULTIVIR-01) using a new

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… Class I major histocompatibility complex-restricted cytotoxic T lymphocytes specific for Epstein-Barr virus (EBV)-transformed B lymphoblastoid cell lines against which they were raised . …

Sirolimus versus cyclosporine in haploidentical stem cell transplantation with posttransplant cyclophosphamide and mycophenolate mofetil as graft-versus-host disease prophylaxis.

Sirolimus has emerged as an alternative to calcineurin inhibitors-based (CNI) graft-versus-host disease (GVHD) prophylaxis. This retrospective study compares the outcome of 133 consecutive adult patients with haematological malignancies undergoing haploidentical stem cell transplantation with posttransplant cyclophosphamide (PTCy) and mycophenolate mofetil (MMF), combined with cyclosporine A (PTCy-CsA-MMF, n = 67) or sirolimus (PTCy-Sir-MMF, n = 66) as GVHD prophylaxis strategy. The median follow-up was 48 (range 22-83) and 13 (range 3-33) months, respectively. PTCy-CsA-MMF was associated in m

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… Durable engraftment of major histocompatibility complex‐incompatible cells after nonmyeloablative conditioning with fludarabine, low‐dose total body irradiation, and posttransplantation cyclophosphamide. Blood. 2001;98:3456–64. 2. Robinson TM, O'Donnell PV, Fuchs EJ, Luznik L. …

Exosomes in the Repair of Bone Defects: Next-Generation Therapeutic Tools for the Treatment of Nonunion.

Nonunion with bone defects, a common complication after long bone fracture, is a major challenge for orthopaedic surgeons worldwide because of the high incidence rate and difficulties in achieving successful treatment. Bone defects are the main complications of nonunion. The conventional biological treatments for nonunion with bone defects involve the use of autologous bone grafts or bone graft substitutes and cell-based therapy. Traditional nonunion treatments have always been associated with safety issues and various other complications. Bone grafts have limited autologous cancellous bone an

Иммунный транскриптомный профиль у взрослых женских свиней: доминантный статус оказывает большее влияние, чем экологическая обогащение.

ОКРУЖАЮЩАЯ СРЕДА: Оценка благосостояния сельскохозяйственных животных имеет решающее значение, однако по-прежнему отсутствуют практические физиологические средства. В этом исследовании мы проверили, обнаруживает ли периферийный транскриптом моноядерной клетки крови (PBMC) вариации в связи с благосостоянием свиней. Для этого мы сравнивали животных, состояние благосостояния которых было расценено как отличающееся из-за их жизни в более или менее обогащенной среде и из-за их различного доминирующего положения. Совы размещались в обычном помещении (C, n = 36) или обогащенного (E, n = 35) среда с д

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… OTUB2 is associated with protein modification, PIK3R6 is associated with the PI3K-AKT signaling pathway, and RNF39 is part of major histocompatibility complex class I. The expression of the uncharacterized gene ( ENSSSCG00000033790 ) was upregulated on both G98 and L12. …

Does the Immunocompetent Status of Cancer Patients Have an Impact on Therapeutic DC Vaccination Strategies?

Although different types of therapeutic vaccines against established cancerous lesions in various indications have been developed since the 1990s, their clinical benefit is still very limited. This observed lack of effectiveness in cancer eradication may be partially due to the often deficient immunocompetent status of cancer patients, which may facilitate tumor development by different mechanisms, including immune evasion. The most frequently used cellular vehicle in clinical trials are dendritic cells (DCs), thanks to their crucial role in initiating and directing immune responses. Viable va

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… Tumors have evolved different evasion mechanisms including: i) downregulation of major histocompatibility complex (MHC) Class I via the inhibition of NLRC5, which is a key transcription cofactor, to avoid T cell recognition [ 42 , 43 ]; ii) expression of surface molecules for T cell suppression, such … In this respect, several chemotherapy agents (cyclophosphamide, oxaliplatin, or gemcitabine) have been shown to increase major histocompatibility complex (MHC) class 1 expression in tumor cells [ 219 ]. …

Dysregulated TRK signalling is a therapeutic target in CYLD defective tumours.

Individuals with germline mutations in the tumour-suppressor gene CYLD are at high risk of developing disfiguring cutaneous appendageal tumours, the defining tumour being the highly organised cylindroma. Here, we analysed CYLD mutant tumour genomes by array comparative genomic hybridisation and gene expression microarray analysis. CYLD mutant tumours were characterised by an absence of copy-number aberrations apart from LOH chromosome 16q, the genomic location of the CYLD gene. Gene expression profiling of CYLD mutant tumours showed dysregulated tropomyosin kinase (TRK) signalling, with overex

Don't Cut the Cord: Why Umbilical Cord Blood Still Deserves a Place in Transplantation.

The use of umbilical cord blood (UCB) as a stem cell source in haematopoietic stem cell transplant (HSCT) has greatly declined in recent years. It has largely been replaced by mismatched unrelated and family donors, facilitated by advances in transplant technologies, including post-transplant cyclophosphamide to prevent graft-versus-host disease (GVHD). UCB remains a distinctive source of haematopoietic stem cells (HSCs) with unique immunologic and practical advantages, including for those with malignant and non-malignant diseases. Compared to other cell sources, UCB transplantation (UCBT) off