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Roles of Microvesicles in Tumor Progression and Clinical Applications.

Microvesicles are extracellular vesicles with diameter ranging from 100 to 1000 nm that are secreted by tumor cells or other cells in the tumor microenvironment. A growing number of studies demonstrate that tumor-derived microvesicles are involved in tumor initiation and progression, as well as drug resistance. In addition, tumor-derived microvesicles carry a variety of immunogenic molecules and inhibit tumor response to immunotherapy; therefore, they can be exploited for use in tumor vaccines. Moreover, because of their high stability, tumor-derived microvesicles extracted from body fluids ca

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… Table 1 Biomarkers of MVs Abbreviations : MVs, microvesicles; ARF6, ADP-ribosylation factors 6; MHC I, major histocompatibility complex class I; VAMP3, vesicle-associated membrane protein 3; CD41, cluster of differentiation 41; CRC, colorectal cancer; TF, tissue factor; EGFR, epithelium growth factor … histocompatibility complex I (MHC I), EMMPRIN, chemokine receptors (CCR6, CX3CR1), and epithelial cell adhesion molecules. …

Overcoming immunosuppression in cancer: how ketogenic diets boost immune checkpoint blockade.

Immune checkpoint blockade (ICB) is now part of the standard of care in the treatment of many forms of cancer, yet it lacks efficacy in some patients, necessitating adjunct therapies to support the anti-tumor immune response. Ketogenic diets (KDs), i.e., high-fat low-carbohydrate diets, have been shown to have antiproliferative and immunomodulatory effects in various preclinical cancer studies. Here, we review current knowledge of the complex interplay of KDs and the anti-tumor immune response in the context of ICB therapy, to update our understanding of diet-induced immunometabolic reprogramm

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… Solid tumors, especially, are poorly penetrated by lymphocytes, for multiple reasons, including absence of neoantigens, low expression of major histocompatibility complex I (MHC-I), and secretion of inhibitory cytokines such as transforming growth factor beta (TGF-β) and interleukin 10 (IL-10) [ 2 ]. … Note: CCL: C–C motif chemokine, CXCL: C-X-C motif chemokine, HDACi: histone deacetylase inhibition, IFN-γ: interferon gamma, MHC-I: major histocompatibility complex 1, PDL-1: programmed cell death ligand 1, TGF-β: transforming growth factor beta, TME: tumor microenvironment. (Created in BioRender. …

Harnessing the Immune System to Fight Multiple Myeloma.

Multiple myeloma (MM) is a heterogeneous plasma cell malignancy differing substantially in clinical behavior, prognosis, and response to treatment. With the advent of novel therapies, many patients achieve long-lasting remissions, but some experience aggressive and treatment refractory relapses. So far, MM is considered incurable. Myeloma pathogenesis can broadly be explained by two interacting mechanisms, intraclonal evolution of cancer cells and development of an immunosuppressive tumor microenvironment. Failures in isotype class switching and somatic hypermutations result in the neoplastic

Non-viral approaches in CAR-NK cell engineering: connecting natural killer cell biology and gene delivery.

Natural Killer (NK) cells are exciting candidates for cancer immunotherapy with potent innate cytotoxicity and distinct advantages over T cells for Chimeric Antigen Receptor (CAR) therapy. Concerns regarding the safety, cost, and scalability of viral vectors has ignited research into non-viral alternatives for gene delivery. This review comprehensively analyses recent advancements and challenges with non-viral genetic modification of NK cells for allogeneic CAR-NK therapies. Non-viral alternatives including electroporation and multifunctional nanoparticles are interrogated with respect to CAR

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… NK cells may identify abnormal cells through downregulation of human leukocyte antigen (HLA), synonymous with major histocompatibility complex (MHC), which are normally expressed on healthy cells, or upregulation of stress-induced ligands, such as major histocompatibility complex class 1 chain-related … major histocompatibility complex class 1 chain-related protein A and B (MICA, MICB). …

Adoptive T-cell therapy for Leukemia.

Allogeneic stem cell transplantation (alloSCT) is the most robust form of adoptive cellular therapy (ACT) and has been tremendously effective in the treatment of leukemia. It is one of the original forms of cancer immunotherapy and illustrates that lymphocytes can specifically recognize and eliminate aberrant, malignant cells. However, because of the high morbidity and mortality that is associated with alloSCT including graft-versus-host disease (GvHD), refining the anti-leukemia immunity of alloSCT to target distinct antigens that mediate the graft-versus-leukemia (GvL) effect could transform

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… Many, but not all, tumor antigens arise from intracellular proteins that must be processed and presented by a cell’s major histocompatibility complex (MHC) in order to trigger TCR-binding and provoke an immune response. … histocompatibility complex Minimal residual disease Minor histocompatibility antigen Multiple myeloma Myelodysplastic syndrome Natural killer cell Non-Hodgkin Lymphoma Partial response Peripheral blood mononuclear cells Post-allogeneic stem cell transplant lymphoproliferative disease Single …

Изучение роли Т клеток в болезни Альцгеймера и других нейродегенеративных заболеваниях: новые терапевтические идеи из Т Клеток на симпозиуме по мозгам.

В этой статье подытоживаются итоги первого симпозиума "Те ячейки в мозгу", проведенного в Колумбийском университете. Эксперты собрались для изучения роли Т клеток в нейродегенеративных заболеваниях. Ключевые темы включали характеристику антигенной иммунной реакции, репертуар T рецептора клеток (TCR), микробную этиологию болезни Альцгеймера (AD) и перекресток клеток микроглиа-Т с уделением особого внимания тому, как Т клетки влияют на нейроинфламмацию и АД биомаркеры, такие как амилоидная бета и тау. На симпозиуме были также рассмотрены иммунотерапии АД, включая исследование валацикловирусного

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… Each T cell is engineered to recognize a specific antigen, usually a peptide fragment bound to the major histocompatibility complex (MHC) on an antigen‐presenting cell. … Aβ, amyloid beta; AD, Alzheimer's disease; ALS, amyotrophic lateral sclerosis; CNS, central nervous system; HLA, human leukocyte antigen; MHC, major histocompatibility complex; PD, Parkinson's disease; TDP‐43, TAR DNA‐binding protein 43. …

Application Of Adoptive Immunotherapy In Ovarian Cancer.

Ovarian cancer (OC) has been the most fatal gynecological disease that threatens women's health. Surgery and platinum-based chemotherapy are the basic ovarian cancer treatments that can improve survival, but the five-year survival rate has not improved because of delayed diagnosis, drug resistance, and recurrence. Novel treatments are needed to improve the prognosis and survival rate of ovarian cancer patients. In recent years, adoptive cell therapy (ACT) has received increasing attention as an emerging therapeutic strategy in the treatment of solid tumors including OC. ACT has shown promising

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… Abbreviations: MHC, major histocompatibility complex; NK, natural killer; LAK, lymphokine-activated killer; CIK, cytokine-induced killer; CAR, chimeric-antigen receptors; TCR, T cell receptors; TIL, tumor-infiltrating lymphocytes. … Abbreviations: MHC, major histocompatibility complex; NK, natural killer; LAK, lymphokine-activated killer; CIK, cytokine-induced killer; CAR, chimeric-antigen receptors; TCR, T cell receptors; TIL, tumor-infiltrating lymphocytes. …

Innovative Clinical Perspectives for CIK Cells in Cancer Patients.

Cytokine-induced killer (CIK) cells are T lymphocytes that have acquired, in vitro, following extensive manipulation by Interferon gamma (IFN-γ), OKT3 and Interleukin 2 (IL-2) addition, the expression of several Natural Killer (NK) cell-surface markers. CIK cells have a dual "nature", due to the presence of functional TCR as well as NK molecules, even if the antitumoral activity can be traced back only to the NK-like structures (DNAM-1, NKG2D, NKp30 and CD56). In addition to antineoplastic activity in vitro and in several in-vivo models, CIK cells show very limited, if any, GvHD toxicity as we

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… Introduction Cytokine-induced killer (CIK) cells are non-MHC (Major Histocompatibility Complex) restricted, cytotoxic antitumoral cells expanded in vitro from circulating precursors. CIK cells share characteristics of both T and NK cells. … Abbreviation: MHC (Major Histocompatibility Complex); GVHD (Graft versus Host Disease); T/NK (T Natural Killer); CIK (Cytokine Induced Killer); T-EMRA (Effector memory T); TCR (T cell receptor); NK (Natural Killer); DNAM1 (DNAX Accessory Molecule-1); LFA1 (Lymphocyte function-associated antigen 1) 1.5 …

Chimeric antigen receptor T‑cell therapy-a hematological success story.

Chimeric antigen receptor (CAR) T cells are genetically engineered autologous cells that express an activating receptor targeted towards one or more tumoral antigens. After ex vivo production and re-infusion, they are able to proliferate in the host and to recognize and kill tumor cells. Together with checkpoint inhibition, this new therapy is already being celebrated as a major medical breakthrough in recent years, due to the substantial benefit observed in clinical trials with patients with chemotherapy-refractory B‑cell malignancies. These results have led to the recent approval of two CAR

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… In contrast to the natural T‑cell response, this process is not major histocompatibility complex (MHC) restricted but only dependent on the presence of the targeted surface antigen, thus, eliminating MHC downregulation as a major mechanism of cancer immune evasion [ 1 ]. … Abbreviations Acute lymphoblastic leukemia Chimeric antigen receptor Cluster of differentiation 19 Chronic lymphocytic leukemia Complete remission Cytokine release syndrome Diffuse large B‑cell lymphoma European Medicines Agency Food and Drug Administration Major histocompatibility complex …

Acute graft-versus-host disease and bronchiolitis obliterans after autologous stem cell transplantation in a patient with multiple myeloma.

Sixty-seven-year-old patient, diagnosed with multiple myeloma who had received autologous stem cell transplantation, following bortezomib, dexamethasone and thalidomide conventional regimen, achieving complete response, developed rash, diarrhea, and severe respiratory failure, 80 days after the transplantation procedure. He was diagnosed with graft-versus-host disease and bronchiolitis obliterans syndrome.

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… It has also been described that CD8 + cells recognize invariant chain fragment peptides (CLIP), which are associated with major histocompatibility complex (MHC) 22 . … histocompatibility complex class II determinants in cyclosporine-induced syngenic graft versus host disease: specificity of cytolytic effect T cells Transplantation 1998 65 785 792 9539089 10.1097/00007890-199803270-00004 Fidler C Klumpp T Mangan K Martin M Sharma M Emmons R Spontaneous graft versus …

Роль микроглии в множественном склерозе: последствия для лечения ингибиторами тиросина Брютона.

Множественный склероз (MS) — хроническое аутоиммунное заболевание, затрагивающее центральную нервную систему (CNS), характеризующееся воспалением и нейродегенерацией. Патофизиология MS, особенно его прогрессивные формы, включает различные клеточные компоненты, включая микроглию, являющиеся основными постоянными иммунными клетками CNS. В настоящем обзоре рассматривается роль микроглии в нейроинфламмации, ремонте тканей и нейронном гомеостазе, а также их участие в MS и изучаются потенциальные терапевтические стратегии, ориентированные на микроглиальную функцию.МЕТОДЫ: Поиск литературы, проведенн

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… BMP4, bone morphogenetic protein 4; CD, cluster of differentiation; IGF-1, insulin-like growth factor 1; MHC, major histocompatibility complex. Figure adapted from Guerrero BL et al. … histocompatibility complex (MHC) class II, ferritin complex, immunoglobulin Fc-γ receptors, and complement component C1 complex ( 35 ). …

Potential Novel Biomarkers in Chronic Graft-Versus-Host Disease.

Prognostic, diagnostic or predictive biomarkers are urgently needed for assessment of chronic graft-versus-host disease (cGvHD), a major risk for patients undergoing allogeneic hematopoietic stem cell transplantation. The main goal of this review generated within the COST Action EUROGRAFT "Integrated European Network on Chronic Graft Versus Host Disease" was to identify potential novel biomarkers for cGvHD besides the widely accepted molecular and cellular biomarkers. Thus, the focus was on cellular biomarkers, alloantibodies, glycomics, endothelial derived particles, extracellular vesicles, m

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… MVB, multivesicular bodies; ESCRT, endosomal sorting complex required for transport; MHC, major histocompatibility complex ( 91 ). …

Autophagy in tumor immune escape and immunotherapy.

The immunotherapy targeting tumor immune escape mechanisms has become a critical strategy in anticancer treatment; however, the challenge of immune resistance remains significant. Autophagy, a cellular response to various stressors, involves the degradation of damaged proteins and organelles via lysosomal pathways, maintaining cellular homeostasis. This process not only supports tumor cell survival but also profoundly impacts the efficacy of cancer immunotherapies. The modulation of autophagy in tumor cells or immune cells exerts dual effects on tumor immune escape and immunotherapy. However,

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… Radiotherapy activates autophagy to increase CD8(+) T cell infiltration by modulating major histocompatibility complex class-I expression in non-small cell lung cancer. J Int Med Res. 2019;47:3818–30. 31187666 10.1177/0300060519855595 PMC6726798 83. … Autophagy facilitates major histocompatibility complex class I expression induced by IFN-γ in B16 melanoma cells. Cancer Immunol Immunother. 2010;59:313–21. 19680649 10.1007/s00262-009-0752-1 PMC11029913 84. …

T-cell receptor-based therapy: an innovative therapeutic approach for solid tumors.

T-cell receptor (TCR)-based adoptive therapy employs genetically modified lymphocytes that are directed against specific tumor markers. This therapeutic modality requires a structured and integrated process that involves patient screening (e.g., for HLA-A*02:01 and specific tumor targets), leukapheresis, generation of transduced TCR product, lymphodepletion, and infusion of the TCR-based adoptive therapy. In this review, we summarize the current technology and early clinical development of TCR-based therapy in patients with solid tumors. The challenges of TCR-based therapy include those associ

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… This approach has been selected for its ability to recognize tumor-specific epitopes presented by the major histocompatibility complex (MHC) molecules on the tumor cell surface (Fig. 2 ). … A single peptide-major histocompatibility complex ligand triggers digital cytokine secretion in CD4(+) T cells. Immunity. 2013;39:846–857. doi: 10.1016/j.immuni.2013.08.036. 17. van der Merwe PA, Dushek O. Mechanisms for T cell receptor triggering. …

Микроглии/Макропатии в области аутоиммунной демьелинизации энцефаломелита (многообразный склероз/нейромиелит Оптика).

Микроглии и макрофаги являются важнейшими посредниками иммунной реакции в центральной нервной системе. Их функции варьируются от гомеостатического обслуживания до патогенеза аутоиммунных демиелинизирующих заболеваний, таких, как множественный склероз и оптический спектр нейромелита. В рамках этого обзора изучаются источники микроглии и макрофаги, а также механизмы их активации, взаимодействие с другими нейронными клетками и вклад в развитие и восстановление заболеваний. В нем также подчеркивается актуальность перевода знаний, полученных с помощью моделей животных, и терапевтический потенциал,

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… histocompatibility complex; P2RY12, purinergic receptor P2Y12; TMEM119, transmembrane protein 119. … Abbreviations: CD, cluster of differentiation; CNS, central nervous system; CX3CR1, CX3C chemokine receptor 1; iNOS, inducible nitric oxide synthase; MHC, major histocompatibility complex; P2RY12, purinergic receptor P2Y12; TMEM119, transmembrane protein 119. …

От диагностики к лечению: изучение механизмов, лежащих в основе оптического неврата в множестве склерозов.

Множественный склероз (MS) — хроническое аутоиммунное заболевание, воздействующее на центральную нервную систему, которое, как правило, вызывает сенсорные расстройства, моторную слабость, слабую походку, несогласованность и оптический неуриит (ON). Согласно статистическим данным, до 50% пациентов, страдающих синдромом MS, испытывают проблемы со зрением в период болезни, страдающие от нечеткого зрения, боли, недостатка зрения и даже слепоты. Лечение перешло от кортикостероидов к лечению, ориентированному на клетки В/Т. В рамках этого обзора проводится всеобъемлющая и систематическая оценка диаг

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… Ig immunoglobulin, CD Cluster of differentiation, TCR T-cell receptor, MHC major histocompatibility complex, Treg regulatory T cell, Breg regulatory B cell, IL Interleukin, GM-CSF granulocyte–macrophage colony-stimulating factor, TNF-α tumor necrosis factor-α, LT lymphotoxin-α, MAC … histocompatibility complex, NF-κB nuclear factor-kappa B, B7 B7 family molecule, CD cluster of differentiation, TCR T-cell receptor, MdC monocyte-derived cells, GM-CSF granulocyte–macrophage colony-stimulating factor, TNF-α tumor necrosis factor-α, MMPs matrix metalloproteinases. …

Effective Immunosurveillance After Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia.

The number of patients receiving allogeneic hematopoietic stem cell transplantation (alloHCT) has increased constantly over the last years due to advances in transplant technology development, supportive care, transplant safety, and donor availability. Currently, acute myeloid leukemia (AML) is the most frequent indication for alloHCT. However, disease relapse remains the main cause of therapy failure. Therefore, concepts of maintaining and, if necessary, reinforcing a strong graft-versus-leukemia (GvL) effect is crucial for the prognosis and long-term survival of the patients. Over the last d

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… NKG2D that binds to major histocompatibility complex class I chain-related protein A and B (MIC A and MIC B) and UL16 binding proteins (ULBPs) is an important activating receptor expressed by NK cells and cytotoxic T-cells alike. 114 The fact that leukemic stem cells often lack NKG2D activating ligands …

Recent advances in renal transplantation: antibody-mediated rejection takes center stage.

Overlooked for decades, antibodies have taken center stage in renal transplantation and are now widely recognized as the first cause of allograft failure. Diagnosis of antibody-mediated rejection has considerably improved with identification of antibody-mediated lesions in graft biopsies and advances made in the detection of circulating donor-specific antibodies. Unfortunately, this progress has not yet translated into better outcomes for patients. Indeed, in the absence of a drug able to suppress antibody generation by plasma cells, available therapies can only slow down graft destruction. Th

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… histocompatibility complex (MHC) molecules. … AMR, antibody-mediated rejection; Conv, convertase; IV, intravenous; MAC, membrane attack complex; MHC, major histocompatibility complex; mTOR, mammalian target of rapamycin; NK, natural killer. …

Harnessing Epigenetic Mechanisms to Overcome Immune Evasion in Cancer: The Current Strategies and Future Directions.

Combining epigenetic alterations with cancer immunotherapy offers a promising approach to improve therapeutic outcomes by targeting the complex biology of tumors. Epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNAs (ncRNAs) play a dual role in maintaining immune homeostasis and promoting cancer progression. Changes like hypomethylation in tumor cells can contribute to immune evasion and treatment resistance. Advances in epigenetic tools, particularly clustered regularly interspaced short palindromic repeat (CRISPR) and their associated protein (Cas9)-based

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… Through DNA methylation and histone changes, tumors downregulate major histocompatibility complex (MHC) and tumor-associated antigens (TAAs), decreasing immune cell recognition. … Tumor-associated antigens (TAAs), major histocompatibility complex molecules, and elements of the antigen processing machinery can all be silenced by DNA methylation and histone changes, which lowers antigen presentation and inhibits cytotoxic T lymphocyte activation. …

Promising immunotherapeutic approaches for primary effusion lymphoma.

Primary effusion lymphoma (PEL) is a large B-cell neoplasm usually presenting as a serious effusion in body cavities without detectable tumor masses. It is an AIDS-related non-Hodgkin's lymphoma (HL) with human herpes virus 8 (HHV8)/Kaposi sarcoma-associated herpes virus (KSHV) infection. A combination antiretroviral therapy (cART) prolongs the lifespan of AIDS and AIDS-related malignant lymphoma patients, but PEL continues to have a dismal prognosis. PEL showed disappointing outcomes with standard chemotherapy such as CHOP or CHOP-like regimens. A PEL status highlights the urgent need for new

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… It is well known that KSHV infection results in major histocompatibility complex class 1 (MHC-I) downregulation during viral lytic replication. … ADCC: antibody-dependent cell cytotoxicity; ADCP: antibody-dependent cell phagocytosis; CAR: chimeric antigen receptor; CTL: cytotoxic T lymphocytes; IL: interleukin; MHC- I: major histocompatibility complex class 1; NK: natural killer; SLAMF7: signaling lymphocytic activation molecule 7; TCR: T cell …