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γδ T cells: origin and fate, subsets, diseases and immunotherapy.

The intricacy of diseases, shaped by intrinsic processes like immune system exhaustion and hyperactivation, highlights the potential of immune renormalization as a promising strategy in disease treatment. In recent years, our primary focus has centered on γδ T cell-based immunotherapy, particularly pioneering the use of allogeneic Vδ2+ γδ T cells for treating late-stage solid tumors and tuberculosis patients. However, we recognize untapped potential and optimization opportunities to fully harness γδ T cell effector functions in immunotherapy. This review aims to thoroughly examine γδ T cell im

Immunotherapy in Acute Myeloid Leukemia: A Literature Review of Emerging Strategies.

In the last twenty years, we have witnessed a paradigm shift in the treatment and prognosis of acute myeloid leukemia (AML), thanks to the introduction of new efficient drugs or approaches to refine old therapies, such as Gemtuzumab Ozogamicin, CPX 3-5-1, hypomethylating agents, and Venetoclax, the optimization of conditioning regimens in allogeneic hematopoietic stem cell transplantation and the improvement of supportive care. However, the long-term survival of non-M3 and non-core binding factor-AML is still dismal. For this reason, the expectations for the recently developed immunotherapies,

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… In 2013, Wiernick et al. observed that CD16 × 33 BiKE and ADAM17 inhibitors can overcome inhibitory signals mediated by class I major histocompatibility complex (MHC) recognition and CD16 clipping, resulting in potent NK cell killing of CD33+ AML targets [ 59 ]. …

Exosomes in oncofertility: emerging roles in chemotherapy-induced reproductive damage and fertility preservation.

ABSTRACT: Oncofertility has emerged as a critical interdisciplinary field addressing the reproductive challenges faced by cancer patients, particularly those undergoing chemotherapy. While chemotherapeutic agents remain indispensable in cancer therapy, their gonadotoxic effects frequently result in diminished ovarian reserve, impaired spermatogenesis, and long-term infertility. Exosomes - small extracellular vesicles enriched with nucleic acids, proteins, and lipids - are increasingly recognized as key mediators of intercellular communication in both pathological and regenerative contexts. Rec

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… Following the seminal discovery by Raposo et al. (1996) that exosomes participate in antigen presentation and acquired immunity, Dexs were developed as cell-free cancer vaccines capable of delivering tumor antigens and major histocompatibility complex (MHC) molecules to elicit antigen-specific T-cell …

Autoantibodies as Biomarker and Therapeutic Target in Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare connective tissue disorder characterized by immune dysregulation evoking the pathophysiological triad of inflammation, fibrosis and vasculopathy. In SSc, several alterations in the B-cell compartment have been described, leading to polyclonal B-cell hyperreactivity, hypergammaglobulinemia and autoantibody production. Autoreactive B cells and autoantibodies promote and maintain pathologic mechanisms. In addition, autoantibodies in SSc are important biomarkers for predicting clinical phenotype and disease progression. Autoreactive B cells and autoantibodies rep

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… An interesting mechanism involves the neonatal Fc receptor (FcRn) which has a structure similar to the major histocompatibility complex (MHC) class I and also associates with β2-microglobulin. The FcRn is involved in the transport of maternal IgG to the fetus. …

Role of Nanomedicine-Based Therapeutics in the Treatment of CNS Disorders.

Central nervous system disorders, especially neurodegenerative diseases, are a public health priority and demand a strong scientific response. Various therapy procedures have been used in the past, but their therapeutic value has been insufficient. The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier is two of the barriers that protect the central nervous system (CNS), but are the main barriers to medicine delivery into the CNS for treating CNS disorders, such as brain tumors, Parkinson's disease, Alzheimer's disease, and Huntington's disease. Nanotechnology-based medicinal

Radiotherapy and cytokines: A systems view of immunotherapy and toxicity (Review).

Radiotherapy (RT) is increasingly recognized as a system‑level immunomodulator capable of reshaping cytokine networks across spatial, temporal and dosimetric dimensions. This review synthesizes existing evidence on RT parameters, key signaling axes, major effector cells, organ‑specific contexts and clinical translation. It describes how the cyclic GMP‑AMP synthase/stimulator of interferon genes (STING)/IFN‑I, NF‑κB and TGF‑β pathways coordinate immune activation and immune suppression after irradiation. It then summarizes macrophage‑centered regulatory circuits and chemokine axes, including C‑

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… The resulting IFN release promotes dendritic cell maturation and major histocompatibility complex class I (MHC-I) upregulation, enhances tumor antigen cross-presentation and elicits antigen-specific cytotoxic T-lymphocyte responses that mediate antitumor efficacy ( 66 , 71 , 72 ). …

Dying of Stress: Chemotherapy, Radiotherapy, and Small-Molecule Inhibitors in Immunogenic Cell Death and Immunogenic Modulation.

Innovative strategies to re-establish the immune-mediated destruction of malignant cells is paramount to the success of anti-cancer therapy. Accumulating evidence suggests that radiotherapy and select chemotherapeutic drugs and small molecule inhibitors induce immunogenic cell stress on tumors that results in improved immune recognition and targeting of the malignant cells. Through immunogenic cell death, which entails the release of antigens and danger signals, and immunogenic modulation, wherein the phenotype of stressed cells is altered to become more susceptible to immune attack, radiother

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… DAMP: damage-associated molecular patterns; TAA: tumor-associated antigen; HMGB1: high-mobility group box 1; ATP: adenosine triphosphate; IFN: interferon; MHC: major histocompatibility complex; TCR: T-cell receptor. …

The role of mesenchymal stem cells in attenuating inflammatory bowel disease through ubiquitination.

Inflammatory bowel disease (IBD), a condition of the digestive tract and one of the autoimmune diseases, is becoming a disease of significant global public health concern and substantial clinical burden. Various signaling pathways have been documented to modulate IBD, but the exact activation and regulatory mechanisms have not been fully clarified; thus, a need for constant exploration of the molecules and pathways that play key roles in the development of IBD. In recent years, several protein post-translational modification pathways, such as ubiquitination, phosphorylation, methylation, acety

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… Xenogeneic immunosuppression of human umbilical cord mesenchymal stem cells in a major histocompatibility complex-mismatched allogeneic acute graft-versus-host disease murine model. Eur J Haematol. (2011) 87:235–43. doi: 10.1111/ejh.2011.87.issue-3 64. …

Необычные хранители мозга: MAIT клетки как новые игроки в иммунитете от глиобластомы.

Глиобластома (GBM) является агрессивной формой рака мозга без лечения. Несмотря на то, что T-клеточная терапия продемонстрировала значительный успех в борьбе с раком крови, их применение для лечения твердых опухолей, включая GBM, затрудняется иммуновосприимчивой микроопухолью и нехваткой целевых показателей по борьбе с опухолью. Существует настоятельная необходимость более глубокого понимания иммунной реакции на ГБМ, с тем чтобы можно было разработать новые терапевтические подходы. Недавно было описано постоянное население мукосальных инвариантов Т (MAIT) в мозгу, которые могут выполнять крити

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… They have limited repertoires of T cell receptors (TCRs), which are restricted to antigen presenting molecules that, unlike the Major Histocompatibility Complex (MHC) Class I and II molecules, have limited polymorphism, thus reducing the likelihood of off-target reactivity. …

Immunotherapies for pediatric cancer: current landscape and future perspectives.

The advent of immunotherapy has revolutionized how we manage and treat cancer. While the majority of immunotherapy-related studies performed to date have focused on adult malignancies, a handful of these therapies have also recently found success within the pediatric space. In this review, we examine the immunotherapeutic agents that have achieved the approval of the US Food and Drug Administration for treating childhood cancers, highlighting their development, mechanisms of action, and the lessons learned from the seminal clinical trials that ultimately led to their approval. We also shine a

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… CAR-T cells are an attractive form of immunotherapy because they can engage tumor cells independently of antigen presentation by the major histocompatibility complex (MHC), which is often downregulated or absent in many cancers as a defense against immune-mediated destruction [ 74 ]. …

Development of CAR T Cell Therapy in Children-A Comprehensive Overview.

CAR T cell therapy has revolutionized immunotherapy in the last decade with the successful establishment of chimeric antigen receptor (CAR)-expressing cellular therapies as an alternative treatment in relapsed and refractory CD19-positive leukemias and lymphomas. There are fundamental reasons why CAR T cell therapy has been approved by the Food and Drug administration and the European Medicines Agency for pediatric and young adult patients first. Commonly, novel therapies are developed for adult patients and then adapted for pediatric use, due to regulatory and commercial reasons. Both strateg

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… The main function and idea of CAR receptors are obviously to enable immune effector cells such as T cells and NK cells to be specifically redirected to cancer cells overexpressing the target antigen in a major histocompatibility complex (MHC)-independent manner [ 38 , 39 ]. scFv-based CAR receptors may …

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of hematologic malignancies: multiple myeloma, lymphoma, and acute leukemia.

Increasing knowledge concerning the biology of hematologic malignancies as well as the role of the immune system in the control of these diseases has led to the development and approval of immunotherapies that are resulting in impressive clinical responses. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a hematologic malignancy Cancer Immunotherapy Guidelines panel consisting of physicians, nurses, patient advocates, and patients to develop consensus recommendations for the clinical application of immunotherapy for patients with multiple myeloma, lymphoma, and acute leukemi

The Evolving Landscape of Immune Regulation and Immunotherapy in Cholangiocarcinoma and Biliary Tract Cancer.

Cholangiocarcinoma (CCA) is an aggressive and molecularly heterogeneous malignancy characterized by a profoundly immunosuppressive tumor microenvironment (TME) and historically limited therapeutic options. Recent advances have redefined the treatment paradigm, with phase III trials establishing chemoimmunotherapy as a standard of care and multi-omic profiling elucidating the interplay between tumor genomics, stromal architecture, and immune regulation. Despite these gains, durable clinical benefit remains confined to a minority of patients, reflecting convergent mechanisms of primary and acqui

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… Major histocompatibility complex (MHC) class I molecules, encoded by human leukocyte antigen (HLA) genes, present intracellular peptides to CD8+ T cells, enabling immune recognition of tumor cells. …

Drug repurposing: A novel strategy to target cancer stem cells and therapeutic resistance.

Chemotherapy is an effortless and frequently used approach in cancer therapy. However, in most cases, it can only prolong life expectancy and does not guarantee a complete cure. Furthermore, chemotherapy is associated with severe adverse effects, one of the major complications of effective cancer therapy. In addition, newly published research outputs show that cancer stem cells are involved in cancer disease progression, drug resistance, metastasis, and recurrence and that they are functional in the trans-differentiation capacity of cancer stem cells to cancer cells in response to treatments.

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… IL-2 eliminates target cells by inducing T-cell expansion with major histocompatibility complex-specific recognition of TAA. 136 However, it can hinder the overall anti-tumor T cell function by up-regulating the CD4 + CD25hi Foxp3 + regulatory T cell (Treg) population and contributes to tumor immunoevasion …

Onco-immunomodulatory properties of pharmacological interference with RAS-RAF-MEK-ERK pathway hyperactivation.

Hyperactivation of the RAS-RAF-MEK-ERK cascade - a mitogen-activated protein kinase pathway - has a well-known association with oncogenesis of leading tumor entities, including non-small cell lung cancer, colorectal carcinoma, pancreatic ductal adenocarcinoma, and malignant melanoma. Increasing evidence shows that genetic alterations leading to RAS-RAF-MEK-ERK pathway hyperactivation mediate contact- and soluble-dependent crosstalk between tumor, tumor microenvironment (TME) and the immune system resulting in immune escape mechanisms and establishment of a tumor-sustaining environment. Consequ

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… The JNK pathway on the other hand was suggested to be involved in the negative selection (apoptosis) of DP thymocytes with insufficient affinity of the pre-TCR to the corresponding major histocompatibility complex (MHC) molecule or autoreactivity to self-antigens ( 28 ). …

Targeting Abnormal Hematopoietic Stem Cells in Chronic Myeloid Leukemia and Philadelphia Chromosome-Negative Classical Myeloproliferative Neoplasms.

Myeloproliferative neoplasms (MPNs) are unique hematopoietic stem cell disorders sharing mutations that constitutively activate the signal-transduction pathways involved in haematopoiesis. They are characterized by stem cell-derived clonal myeloproliferation. The key MPNs comprise chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). CML is defined by the presence of the Philadelphia (Ph) chromosome and BCR-ABL1 fusion gene. Despite effective cytoreductive agents and targeted therapy, complete CML/MPN stem cell eradication is r

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… IFN-α-mediated increase in expression of major histocompatibility complex (MHC) class I molecules and tumour-associated antigens cause reactivation of CTL and prompt CTL-mediated cytotoxicity against LSCs [ 54 , 55 ]. …

Fine-Tuning through Generations: Advances in Structure and Production of CAR-T Therapy.

Chimeric antigen receptor (CAR)-T cell therapy is a promising form of immunotherapy that has seen significant advancements in the past few decades. It involves genetically modifying T cells to target cancer cells expressing specific antigens, providing a novel approach to treating various types of cancer. However, the initial success of first-generation CAR-T cells was limited due to inadequate proliferation and undesirable outcomes. Nonetheless, significant progress has been made in CAR-T cell engineering, leading to the development of the latest fifth-generation CAR-T cells that can target m

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… This extraordinary discovery prompted researchers to consider if it is feasible to genetically design T cells with receptors that could detect a specific antigen independent of a major histocompatibility complex (MHC) expression. …

Применение мезенхимальных ячеек и их эксзоом в нейродегенеративных заболеваниях и лизосомных заболеваниях.

Мезенхимальные стромальные клетки (МСЦ) стали перспективной терапевтической платформой для расстройств центральной нервной системы, включая нейродегенеративные заболевания и лизосомные расстройства хранения (ЛСД). В настоящем обзоре рассматриваются механизмы КБМ, связанные с активностью паракрина, иммуномодуляцией, воздействием антиоксидантов, регулированием с помощью ТФЭБ, а также с ферментатической перекрестной корректировкой в ЛСД, хотя и критически оцениваются проблемы перевода. Мы проводим сравнительный анализ источников КБМ, административных маршрутов, дозирующих режимов и характеристик

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… Major histocompatibility complex (MHC) molecules are virtually absent on their membrane, making MSC-EVs minimally immunogenic and allowing the creation of allogeneic products without the need for donor matching or immunosuppression [ 168 ]. …

Efficacy and safety of antibody-drug conjugates in HER2-positive and HER2-low advanced gastric cancer: a systematic review and update.

PURPOSE: Gastric cancer is a highly prevalent malignancy of the digestive tract in China. Conventional chemotherapeutic drugs and human epidermal growth factor receptor 2 (HER2)‑targeted agents such as trastuzumab remain limited by significant challenges in the treatment of GC, including high rates of drug resistance, significant toxicity and adverse effects, and suboptimal tolerability. The advent of antibody-drug conjugates (ADCs) has marked a paradigm shift in the therapeutic landscape. This review systematically summarises the structural design, mechanisms of action, and current clinical a

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… Preclinical studies have demonstrated that ADCs upregulate PD‑L1 and major histocompatibility complex class I (MHC‑I) on tumor cells, and that the combination of these agents with immunotherapy yields synergistic antitumor activity [ 63 ]. …

Advances in the clinical application of bispecific antibodies in cancer therapy.

Cancer immunotherapy has emerged as one of the most groundbreaking advancements. However, the tumor microenvironment (TME) is often dominated by various immunosuppressive factors, compromising the efficacy of single-target therapies, leading to non-responsiveness or resistance. Bispecific antibodies (BsAbs) represent an innovative immunotherapeutic strategy with enormous potential for improving cancer treatment outcomes. Unlike monoclonal antibodies, BsAbs can concurrently inhibit multiple pro-tumor pathways, target immune checkpoints to mitigate resistance, and bind to two distinct antigens,

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… CD3-engaging BsAbs (T cell engagers) These BsAbs simultaneously bind a TAA and CD3ε on T cells, bridging cytotoxic lymphocytes to tumor cells and inducing major histocompatibility complex (MHC)-independent killing. This mechanism leads to potent T cell activation and tumor lysis. …