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Senescent immune cells in the tumor microenvironment: emerging insights into cancer immunotherapy resistance.

Cancer remains a leading cause of mortality worldwide, with rising incidence and death rates continuing to rise. While conventional treatments such as surgery, radiotherapy, and chemotherapy form the backbone of cancer care, they are often limited by adverse effects, recurrence risk, and incomplete tumor eradication. Tumor immunotherapy-particularly immune checkpoint inhibitors and chimeric antigen receptor (CAR) T cell therapy-has emerged as a transformative approach by activating and reprogramming anti-tumor immune responses. Despite these advances, significant challenges persist, including

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… Upon stimulation by major histocompatibility complex class I (MHC-I), CD8 + T cells secrete interferon-γ (IFN-γ), perforin, and granzymes to eliminate tumor cells. Natural killer (NK) cells similarly mediate tumor cell lysis by releasing cytotoxic molecules. … histocompatibility complex Matrix metalloproteinases Mammalian target of rapamycin complex Natural killer Natural killer receptors Non-small cell lung cancer Programmed cell death protein 1 Programmed death-ligand 1 Phosphatidylinositol-3-kinase Poly(lactic-co-glycolic acid) Poly-L-lysine …

The pleiotropic effects of erythropoietin in infection and inflammation.

Erythropoietin (EPO) is a multi-functional cytokine, which exerts erythropoietic effects but also carries anti-apoptotic and immune-modulatory activities upon binding to two distinct receptors which are expressed on erythroid, parenchymal and immune cells, respectively. Whereas EPO ameliorates hemolytic anemia in malaria or trypanosomiasis and improves the course of autoimmune diseases such as inflammatory bowel disease or autoimmune encephalomyelitis, it deleteriously inhibits macrophage functions in Salmonella infection in animal models. Thus, the specific modulation of extra-erythropoietic

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… Iron homeostasis is also a key determinant of macrophage functions, on the one hand via promoting ROS formation, while on the other hand iron loading of macrophage inhibits pro-inflammatory, LPS- and IFN-γ-driven immune effector pathways such as iNOS, TNF-α or major histocompatibility complex ( MHC ) …

Воздействие метаболического синдрома на нейроинфламму и мозговой барьер.

Метаболический синдром, который включает диабет и ожирение. one из самых распространенных медицинских заболеваний. Она вызывает системное воспаление, приводящее к далеко идущим последствиям для тела, которое все еще обнаруживается. Neuropathology, вызванная метаболическим синдромом, часто является результатом повышения проницаемости кровеносного мозга (ББД). ББД, система, предназначенная для ограничения проникновения токсинов, иммунных клеток и патогенов в мозг, имеет жизненно важное значение для надлежащей нейронной функции. Местное и системное воспаление, вызванное ожирением или типом 2 Мели

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… For example, chronic intracerebral infusion of VEGF in mice was found to upregulate ICAM-1 and major histocompatibility complex I and II, increasing the opportunity for immune response ( Proescholdt et al., 1999 ). …

Многоцелевые лекарственные препараты: новые 2025 и послерыночного контроля за безопасностью наркотиков, 2022-2024.

Полифармакология предназначена для развития соединений, действующих по крайней мере на two целевые показатели (многоцелевые лиганды, МТДЛ). В 2025, Европейское агентство по медицине (ЕМА), 38 наркотиков, и 11 из них были MTDL. Большинство из них - антитела-наркотики, биконкретные антитела или ингибиторы киназы, все из которых указаны для лечения опухолей, включая датопотамаб дерукстекан (гормон-позитивный рецептор, HER2-negative Рак молочной железы), тизотумаб ведотин (сокращенная шейная карцинома), линвосельтамб (четвёртая линия лечения множественной миеломы) и эрдафитиниб (сокращенная уротел

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… This results in T-cell activation and lysis of targeted cells, regardless of the major histocompatibility complex (MHC) class I molecules on antigen-presenting cells or T-cell receptor specificity [ 33 ]. … histocompatibility complex Multiple myeloma Monomethyl auristatin E Magnetic resonance imaging Multi-target-directed ligand(s) Mammalian target of rapamycin serine/threonine protein kinase Neurofibromin 1 gene Non-small cell lung cancer Neurotrophic receptor tyrosine kinase p -aminobenzoic …

High levels of serum β2-microglobulin predict severity of coronary artery disease.

BackgroundThe identification of new risk factors for coronary artery disease (CAD) is increasingly sought in an effort to tackle this threatening disease. β2-microglobulin (B2M) is reported to associate with peripheral arterial disease and adverse cardiovascular outcomes. However, the association between B2M and cardiovascular disease remains under-researched. This study evaluated the effects of B2M on CAD without renal dysfunction.MethodsOne thousand seven hundred sixty-two subjects (403 non-CAD subjects and 1,359 CAD subjects) were investigated. Fasting samples were collected to determine B2

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… β2-microglobulin (B2M), a low molecular-weight protein (~11,800 Da), is a component of the major histocompatibility complex (MHC) class I molecules on all nucleated cells [ 10 ]. …

Current landscape and future directions of targeted-alpha-therapy for glioblastoma treatment.

Glioblastoma (GB) is the most aggressive malignancy of the central nervous system. Despite two decades of intensive research since the establishment of the standard of care, emerging strategies have yet to produce consistent satisfactory outcomes. Because of its specific localisation and intricate characteristics, GB is a uniquely regulated solid tumour with a strong resistance to therapy. Advances in targeted radionuclide therapy (TRT), particularly with the introduction of a-emitting radionuclides, have unveiled potential avenues for the management of GB. Recent preclinical and clinical stud

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… However, GL261 cells have a high mutational load and display strong immunogenicity due to elevated major histocompatibility complex I (MHC-I) expression compared to human GB 150 , which may lead to a more robust adaptive immune response following TAT. … histocompatibility complex I magnetic resonance imaging maximum tolerated dose near-infrared neurokinin type 1 receptor poly(ADP-ribose) polymerase programmed cell death protein 1 programmed death-ligand 1 patient-derived xenograft peptide receptor radionuclide therapy prostate-specific membrane …

Cytotoxic CD4+ T cells: origin, biological functions, diseases and therapeutic targets.

Cytotoxic CD4+ T lymphocytes are a unique subset of CD4+ T cells characterized by their cytokine secretion and cytolytic activity. Unlike traditional CD4+ helper T cells, cytotoxic CD4+ T lymphocytes exhibit similar cytotoxicity to that of CD8+ T cells, revealing unexpected plasticity in CD4+ T-cell functions. This flexibility suggests that CD4+ T cells can transform and acquire effector functions beyond their conventional functions, emphasizing their importance in various immune responses. Despite the identification of cytotoxic CD4+ T lymphocytes decades ago, recent advancements have broaden

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… They are broadly classified into CD4⁺ and CD8⁺ subsets according to the type of major histocompatibility complex (MHC) molecules they recognize. … MHC major histocompatibility complex, Th helper T, IFN-γ interferon-γ, KARs killer activation receptors, IL-15 interleukin-15, cDC1s type 1 conventional dendritic cells. …

Дисфункция мозгового барьера (BBB) в заболеваниях CNS: уделение внимания перицитам.

Дизфункция мозгового барьера (BBB) является важным патологическим механизмом в заболеваниях центральной нервной системы (CNS) и может вызвать ряд патологических реакций, таких, как нейроинфламмационная реакция, окислительный стресс, иммунная инфильтрация и т.д., что усугубляет повреждение мозга. Вместе с тем исследователи часто игнорируют перициты, и ни одно обзорное исследование пока еще не подытожило механизм, с помощью которого перициты способствуют дисфункции ББД в заболеваниях КНС.Поэтому в настоящем обзоре изучается патофизиология дисфункции ББД в связи с заболеваниями КНС и содержится п

Mechanisms of cytokine release syndrome and neurotoxicity of CAR T-cell therapy and associated prevention and management strategies.

Chimeric antigen receptor (CAR) T-cell therapy has yielded impressive outcomes and transformed treatment algorithms for hematological malignancies. To date, five CAR T-cell products have been approved by the US Food and Drug Administration (FDA). Nevertheless, some significant toxicities pose great challenges to the development of CAR T-cell therapy, most notably cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Understanding the mechanisms underlying these toxicities and establishing prevention and treatment strategies are important. In this r

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… Genetically engineered to express CAR molecules that can specifically recognize tumor antigens, CAR T-cells can be activated, proliferate and exert antitumor effects without major histocompatibility complex (MHC) restriction. … Abbreviations Chimeric antigen receptor US Food and Drug Administration Cytokine release syndrome Immune effector cell associated neurotoxicity syndrome Acute lymphocyte leukemia B cell maturation antigen Relapse or refractory multiple myeloma Major histocompatibility complex American Society …

Prospects for Development and Commercialisation of Allogeneic CAR-Based Therapies for Autoimmune Disease.

Chimeric antigen receptor (CAR)-T cell therapies represent a promising therapeutic approach for refractory autoimmune diseases. Although autologous CAR-T cells have achieved success thus far, they require expensive, individualised manufacturing, limiting their commercialisation potential. Allogeneic alternatives could overcome these scalability barriers, providing 'off-the-shelf' treatments, although they raise the issues of graft-vs-host reactions and host-mediated rejection. To mitigate such risks, gene-edited αβ T cells or non-alloreactive host cells (e.g., NK cells, γδ T cells) may be used

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… This structure contrasts with a typical αβ T cell receptor (TCR), which recognises a processed antigen-derived peptide that is presented in the context of a Major Histocompatibility Complex (MHC) molecule. … An alternative, non-genome-editing method involves the manufacture of CAR therapies from ‘unconventional’ T cell subsets instead of αβ T cells, such as Natural Killer (NK) or Gamma Delta (γδ) cells, that recognise target cells in a Major Histocompatibility Complex (MHC)-independent manner, mitigating …

Cytokine-induced killer (CIK) cells: from basic research to clinical translation.

The accumulation of basic researches and clinical studies related to cytokine-induced killer (CIK) cells has confirmed their safety and feasibility in treating malignant diseases. This review summarizes the available published literature related to the biological characteristics and clinical applications of CIK cells in recent years. A number of clinical trials with CIK cells have been implemented during the progressive phases of cancer, presenting potential widespread applications of CIK cells for the future. Furthermore, this review briefly compares clinical applications of CIK cells with th

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… CD3 + CD56 + cells, which are derived from CD3 + CD56 − T cells, are also called natural killer T (NKT) cells and are primarily responsible for non-major histocompatibility complex (MHC)-restricted antitumor activity [ 19 , 20 ]. …

Ксантин Оксидореводаза: Меч с двойным отростком в неврологических заболеваниях.

Неинфекционные неврологические расстройства являются второй основной причиной смерти, и их бремя продолжает расти по мере роста и старения населения мира. Окисляющий стресс и воспаление во многом связаны с активацией и развитием множественных склерозов, болезни Альцгеймера, амиотропического бокового склероза, болезни Хантингтона, болезни Паркинсона и даже инсульта. В ходе этого обзора мы изучаем роль деятельности и продуктов " xanthine oxidoreducase " (XOR) во всех вышеупомянутых неврологических заболеваниях. Редоксальный дисбаланс, вызывающий окислительный стресс, может возникнуть и

Potentiation of natural killer cells to overcome cancer resistance to NK cell-based therapy and to enhance antibody-based immunotherapy.

Natural killer (NK) cells are cellular components of the innate immune system that can recognize and suppress the proliferation of cancer cells. NK cells can eliminate cancer cells through direct lysis, by secreting perforin and granzymes, or through antibody-dependent cell-mediated cytotoxicity (ADCC). ADCC involves the binding of the Fc gamma receptor IIIa (CD16), present on NK cells, to the constant region of an antibody already bound to cancer cells. Cancer cells use several mechanisms to evade antitumor activity of NK cells, including the accumulation of inhibitory cytokines, recruitment

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… One of the peculiarities of NK cells is their capacity to kill target cells without requiring their prior sensitization and the expression of major histocompatibility complex (MHC) molecules on cancer cells ( 17 ). … Clinical significance of soluble major histocompatibility complex class I chain-related in a renal cell carcinoma patients. Asian Pac J Cancer Prev (2013) 14:5651–5. doi: 10.7314/apjcp.2013.14.10.5651 41. Wang LP, Niu H, Xia YF, Han YL, Niu P, Wang HY, et al. …

Cancer metastasis to the bone: Mechanisms and animal models (Review).

The majority of cancer-related deaths result from tumor metastasis, with bone metastasis occurring in almost all types of malignant tumors. Understanding the mechanism by which tumors metastasize to bone is critical for the identification of novel therapeutic targets. A large amount of research has been carried out using animal models, and these models have been crucial in advancing the fundamental understanding of cancer. However, current models are limited; although they can mimic specific stages of the metastatic process, they are not able to replicate the entire process from tumorigenesis

Role of autophagy in cholangiocarcinoma: An autophagy-based treatment strategy.

Cholangiocarcinomas (CCAs) are diverse biliary epithelial tumours involving the intrahepatic, perihilar and distal parts of the biliary tree. The three entirely variable entities have distinct epidemiology, molecular characteristics, prognosis and strategy for clinical management. However, many cholangiocarcinoma tumor-cells appear to be resistant to current chemotherapeutic agents. The role of autophagy and the therapeutic value of autophagy-based therapy are largely unknown in CCA. The multistep nature of autophagy offers a plethora of regulation points, which are prone to be deregulated and

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… Major histocompatibility complex (MCH) I/II Ag presentation is closely regulated by autophagy mechanism, as well as the cellular apoptosis. The multi-roles of autophagy gave the opportunity for the development of antitumor agents that induce this mechanism. …

Bispecific and multispecific T-cell engagers: advancing the future of immunotherapy.

T-cell engagers (TCEs) represent an emerging class of immunotherapies that harness T cells' cytotoxic power to eliminate diseased cells-a transformative future therapeutic strategy. TCEs form immunological synapses to trigger potent immune responses, with proven efficacy in blood cancers; research expands their use to solid tumors via innovative molecular design and improved safety profiles. Beyond oncology, TCEs hold promise in autoimmune disorders by eliminating autoreactive cells, offering novel avenues for diseases like lupus. However, achieving optimal outcomes without disrupting immune h

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… This physical tethering forms immunological synapses, mimicking natural T-cell activation while bypassing the need for antigen presentation via major histocompatibility complex (MHC) molecules. …

Enhancing CAR T cells function: role of immunomodulators in cancer immunotherapy.

CAR T-cell therapy is a promising immunotherapy, providing successful results for cancer patients who are unresponsive to standard and traditional therapeutic approaches. However, there are limiting factors which create a hurdle in the therapy performing its role optimally. CAR T cells get exhausted, produce active antitumor responses, and might even produce toxic reactions. Specifically, in the case of solid tumors, chimeric antigen receptor T (CAR-T) cells fail to produce the desired outcomes. Then, the need to use supplementary agents such as immune system modifying immunomodulatory agents

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… When the antigen-binding domain binds to the tumor-associated antigen (TAA), activation of CAR T cells occurs in a major histocompatibility complex (MHC)-independent fashion, although some CAR T cells can activate in an MHC-dependent manner [ 15 ]. …

Osteocytes: New Kids on the Block for Cancer in Bone Therapy.

The tumor microenvironment plays a central role in the onset and progression of cancer in the bone. Cancer cells, either from tumors originating in the bone or from metastatic cancer cells from other body systems, are located in specialized niches where they interact with different cells of the bone marrow. These interactions transform the bone into an ideal niche for cancer cell migration, proliferation, and survival and cause an imbalance in bone homeostasis that severely affects the integrity of the skeleton. During the last decade, preclinical studies have identified new cellular mechanism

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… In this regard, myeloma cells produce 2-deoxy-D-ribose (2DDR), which activates the major histocompatibility complex class II transactivator (CIITA) in osteocytes [ 80 ]. …

Нацеливание микроглиа-Тх17 на петлю питания вперёд для подавления аутоиммунной нейроинфламмации.

Microglia и TH17 являются основными иммунопатогенными клетками в множестве склероза и его животной модели иммунных аспектов, экспериментального аутоиммунного энцефаломиелита (EAE). Хотя исследования выявили различные роли микроглий и TH17 клеток в EAE, остается неясным, может ли микроглия как потенциальные профессиональные антигенопредставляющие клетки активировать и стабилизировать программу воздействия EAE-патогенных клеток TH17 в vivo; и если да, то может ли TH17, в свою очередь, усилить активное состояние микроглии. Наши данные показывают в целом ряде моделей мыши, включая активные/пассивн

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… Error bars denote the mean ± SEM, ns = not significant, * p  < 0.05, ** p  < 0.01 and *** p  < 0.001 Further analysis showed that ACT001 treatment led to reduced expression of major histocompatibility complex class II (MHC-II) (Fig.  4 C, D) and iNOS (Fig. S5 C, D) compared to the control group. …

Immunosuppression in Glomerular Diseases: Implications for SARS-CoV-2 Vaccines and COVID-19.

BackgroundGlomerular diseases (GD) are chronic conditions that often involve immune dysfunction and require immunosuppressive therapy (IST) to control underlying pathogenesis. Unfortunately, such diseases appear to heighten risks of severe outcomes in COVID-19 and predispose to other infections that may be life-threatening. Thus, averting preventable infections is imperative in GD patients.SummaryThe advent of vaccines demonstrated to be safe and efficacious against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has favorably impacted the COVID-19 pandemic epidemiology. However,