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Targeting Tumor Microenvironment for Cancer Therapy.

Cancer development is highly associated to the physiological state of the tumor microenvironment (TME). Despite the existing heterogeneity of tumors from the same or from different anatomical locations, common features can be found in the TME maturation of epithelial-derived tumors. Genetic alterations in tumor cells result in hyperplasia, uncontrolled growth, resistance to apoptosis, and metabolic shift towards anaerobic glycolysis (Warburg effect). These events create hypoxia, oxidative stress and acidosis within the TME triggering an adjustment of the extracellular matrix (ECM), a response

33rd Annual Meeting & Pre-Conference Programs of the Society for Immunotherapy of Cancer (SITC 2018) : Washington, D.C., USA. 7-11 November 2018.

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Окисляющие молекулярные сигнатуры в неизлечимых заболеваниях: систематический обзор комплексных подходов к машинному обучению и системной биологии.

Окисляющий стресс является одним из основных факторов патогенеза иммунных заболеваний в результате его воздействия на клеточный метаболизм, митохондриальную функцию, иммунную сигнализацию и воспалительную травму тканей. Разрушение гомеостазиса способствует метаболическому перепрограммированию и постоянной активации врожденной и адаптивной иммунной реакции, что способствует прогрессированию заболеваний через многочисленные подстрекательские и аутоиммунные расстройства. Последние достижения в области высокопроизводительных молекулярных технологий привели к созданию крупномасштабных многомерных н

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… Abbreviations: ROS, reactive oxygen species; RNS, reactive nitrogen species; NF-κB, nuclear factor kappa B; IL, interleukin; TNF-α, tumor necrosis factor alpha; MHC-I, major histocompatibility complex class I; GSH, reduced glutathione; GSSG, oxidized glutathione; ETC, electron transport chain; ER, endoplasmic …

Cellular based treatment modalities for unresectable hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver and is unfortunately associated with an overall poor prognosis and high mortality. Early and intermediate stages of HCC allow for treatment with surgical resection, ablation and even liver transplantation, however disease progression warrants conventional systemic therapy. For years treatment options were limited to molecular-targeting medications, of which sorafenib remains the standard of care. The recent development and success of immune checkpoint inhibitors has proven to be a breakthrough in the treatment of

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… The extracellular portion is a single chain antigen recognition receptor composed of heavy and light chains of a monoclonal antibody specific to the tumor surface antigen, allowing for no restrictions of target antigen recognition by major histocompatibility complex (MHC) molecules. …

Emerging roles for the IL-6 family of cytokines in pancreatic cancer.

Pancreatic cancer has one of the poorest prognoses of all malignancies, with little improvement in clinical outcome over the past 40 years. Pancreatic ductal adenocarcinoma is responsible for the vast majority of pancreatic cancer cases, and is characterised by the presence of a dense stroma that impacts therapeutic efficacy and drives pro-tumorigenic programs. More specifically, the inflammatory nature of the tumour microenvironment is thought to underlie the loss of anti-tumour immunity and development of resistance to current treatments. Inflammatory pathways are largely mediated by the exp

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… These cells express low levels of both α-SMA and IL-6, and instead express high levels of major histocompatibility complex class II (MHCII) and related genes [ 43 ]. As such, all three subtypes are transcriptionally and functionally distinct. …

Cell Therapy for Colorectal Cancer: The Promise of Chimeric Antigen Receptor (CAR)-T Cells.

Colorectal cancer (CRC) is a global public health problem as it is the third most prevalent and the second most lethal cancer worldwide. Major efforts are underway to understand its molecular pathways as well as to define the tumour-associated antigens (TAAs) and tumour-specific antigens (TSAs) or neoantigens, in order to develop an effective treatment. Cell therapies are currently gaining importance, and more specifically chimeric antigen receptor (CAR)-T cell therapy, in which genetically modified T cells are redirected against the tumour antigen of interest. This immunotherapy has emerged a

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… These cells share functional and phenotypic properties with NK and T cells and are characterised by rapid expansion ex vivo, non-major histocompatibility complex (MHC)-restricted tumour-killing activity, strong antitumour activity and minimal toxicity [ 17 , 18 ]. …

Immune evasion in cancer: mechanisms and cutting-edge therapeutic approaches.

Immune evasion represents a significant challenge in oncology. It allows tumors to evade immune surveillance and destruction, thereby complicating therapeutic interventions and contributing to suboptimal patient outcomes. This review addresses the critical need to understand how cancers evade immune surveillance. It aims to provide a comprehensive overview of strategies of tumors to escape immune detection by examining tumor-induced immune suppression, immune checkpoint regulation, and genetic and epigenetic influences. Moreover, it explores the dynamic role of the tumor microenvironment (TME)

Cytokine-Engineered Chimeric Antigen Receptor-T Cell Therapy: How to Balance the Efficacy and Toxicity.

Chimeric antigen receptor (CAR)-T cell immunotherapy has revolutionized the paradigm in hematological malignancies. However, its efficacy in treating solid tumors remains limited because the immunosuppressive tumor microenvironment (ITME) seriously blocks T cell activation, infiltration, and proliferation. Cytokines, driving potent assisted function by enhanced T cell expansion, persistence, and direct tumor cell killing, have long been acknowledged as promising candidates combined with CAR-T cells to improve treatment outcomes. Despite their preclinical success, significant toxicity occurs in

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… histocompatibility complex matrix metalloproteinases mesenchymal stromal cells murine stem cell virus mesothelin metyrosine membrane‐type serine protease 1 nuclear translocation of nuclear factor of activated T cells nuclear factor‐κB non‐Hodgkin lymphoma natural killer cells oncolytic adenovirus … The molecular design of CAR confers the capacity for specific tumor cell recognition and major histocompatibility complex (MHC)‐unrestricted cytolytic activity. …

Recent advances in CAR-MSCs: the new engine of cellular immunotherapy evolution.

In recent years, the development of chimeric antigen receptor (CAR) technology has greatly promoted the progress of cellular immunotherapy. Among them, CAR-T cell therapy has shown remarkable clinical effects in the treatment of hematological malignancies. However, this therapy still faces a series of challenges, including immunogenicity, toxic side effects, and insufficient maintenance of long-term efficacy. The latest research progress has extended CAR technology to mesenchymal stem cells (MSCs), and the resulting CAR-MSCs combine the precise targeting ability of CAR molecules with the inher

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… The scFv, derived from antibody variable regions, binds tumor cell surface antigens independently of major histocompatibility complex (MHC). The hinge region connects the scFv to the transmembrane domain. … histocompatibility complex Multiple myeloma Mammalian target of rapamycin Mesenchymal stem cells Nuclear factor kappa-light chain enhancer of activated B cells Nuclear factor erythroid 2 Neuroglial antigen 2 Natural killer Neural progenitor cells Oncolytic adenovirus Overall survival Perinatal …

Immunotherapy for precision medicine in colorectal cancer.

IntroductionColorectal cancer (CRC) is the fourth most common cancer and second leading cause of cancer-related death in the United States. The implementation of CRC screening has decreased CRC incidence in adults older than 65 years. However, among young adults who experience more aggressive disease progression, CRC incidence has been increasing for decades. Immunotherapy represents a collection of innovative and promising approaches with greater efficacy and safety. In this review, we discuss modalities and selected targets of immunotherapies for CRCs that are guided by precision medicine.Ar

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… After processing, antigen fragments are loaded onto major histocompatibility complex (MHC) class I and class II molecules. In addition to antigen processing and loading onto MHC, dendritic cell maturation is also required [ 102 ]. …

Одноклеточная транскриптомика для иммунного профилирования цереброспинной жидкости в неврологических заболеваниях.

В ходе этого всеобъемлющего обзора мы прорабатываем значительный объем исследований по одноклеточной транскриптомике в цереброспайнальной жидкости (CSF) для понимания неврологических заболеваний с аутоиммунным, нейродегенеративным, инфекционным или онкогенным происхождением. Мы тщательно изучаем все опубликованные исследования в этих областях с особым акцентом на множественный склероз, болезнь Альцгеймера и болезнь Паркинсона. Что касается этих заболеваний, то мы анализируем результаты, связанные с иммунными клетками, проникающими в мозг, на основе вскрытого анализа тканей мозга и с использова

Премии победителей и резюме 32nd Ежегодный симпозиум Общества протеинов; Бостон, ОЭТ, июль 9-12, 2018.

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CAR T Cell Therapy of Non-hematopoietic Malignancies: Detours on the Road to Clinical Success.

Chimeric antigen receptor (CAR)-engineered T cells represent a breakthrough in personalized medicine. In this strategy, a patient's own T lymphocytes are genetically reprogrammed to encode a synthetic receptor that binds a tumor antigen, allowing T cells to recognize and kill antigen-expressing cancer cells. As a result of complete and durable responses in individuals who are refractory to standard of care therapy, CAR T cells directed against the CD19 protein have been granted United States Food and Drug Administration (FDA) approval as a therapy for treatment of pediatric and young adult acu

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… CARs are synthetic molecules that combine the effector functions of T cells with the ability of antibodies to detect pre-defined antigens with a high degree of specificity in a non-major histocompatibility complex (MHC) restricted manner ( 20 ). …

Chemokines and their receptors in oral squamous cell carcinoma: mechanisms, clinical significance, and therapeutic implications.

Chemokines, a category of cytokines exhibiting chemotactic properties, have been thoroughly investigated as targets in cancer treatment in recent decades. In oral squamous cell carcinoma (OSCC), a prevalent and high-risk malignancy of the head and neck, chemokines interact with their specific receptors to initiate downstream signaling pathways. This signaling influences not only tumor cell proliferation, migration, invasion, and metastasis of oral cancer cells but also angiogenesis and vascular maturation. Furthermore, they modulate the tumor microenvironment (TME), which consists of diverse c

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… CTLs, which recognize cancer cells presenting major histocompatibility complex class I (MHC-I) molecules, have long been considered the principal lymphocyte subset responsible for tumor cell killing ( 126 ). …

Leveraging the bacteria for enhanced cancer immunotherapy: from a perspective of synthetic biology.

In recent years, synthetic biology has been widely applied to engineer and program cellular behaviors. Using this approach, bacteria can be designed to express immunotherapeutic agents, improve tumor targeting, and deliver therapeutic payloads directly to tumor sites. To further improve efficacy, strategies such as hypoxia-responsive promoters, bacterial swarming, and extracellular vesicles (EVs) have been investigated, along with the synergistic effects of combining bacterial therapy with other treatments (e.g., photodynamic therapy, chemotherapy, immune checkpoint inhibitors). This review su

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… Upon encountering bacteria, DCs present antigens on major histocompatibility complex (MHC) molecules to T cells. These antigens include tumor-associated or tumor-specific antigens expressed by malignant cells, as well as bacterial antigens. …

Immune-Mediated Dermatoses in Patients with Haematological Malignancies: A Comprehensive Review.

Haematological malignancies induce important alterations of the immune system, which account for the high frequency of autoimmune complications observed in patients. Cutaneous immune-mediated diseases associated with haematological malignancies encompass a heterogeneous group of dermatoses, including, among others, neutrophilic and eosinophilic dermatoses, autoantibody-mediated skin diseases, vasculitis and granulomatous dermatoses. Some of these diseases, such as paraneoplastic pemphigus, are associated with an increased risk of death; others, such as eosinophilic dermatoses of haematological

Targeted immunotherapy: harnessing the immune system to battle multiple myeloma.

Multiple myeloma (MM) remains an incurable hematological malignancy disease characterized by the progressive dysfunction of the patient's immune system. In this context, immunotherapy for MM has emerged as a prominent area of research in recent years. Various targeted immunotherapy strategies, such as monoclonal antibodies, antibody-drug conjugates, bispecific antibodies, chimeric antigen receptor T cells/natural killer (NK) cells, and checkpoint inhibitors have been developed for MM. This review aims to discuss promising experimental and clinical evidence as well as the mechanisms of action u

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… CAR chimeric antigen receptor, PD-L1 programmed death-ligand 1, PD-1 programmed cell death protein 1, TCR T cell receptor, MHC major histocompatibility complex, NK cell natural killer cell. …

From Molecular Precision to Clinical Practice: A Comprehensive Review of Bispecific and Trispecific Antibodies in Hematologic Malignancies.

Multispecific antibodies have redefined the immunotherapeutic landscape in hematologic malignancies. Bispecific antibodies (BsAbs), which redirect cytotoxic T cells toward malignant targets via dual antigen engagement, are now established components of treatment for diseases such as acute lymphoblastic leukemia (ALL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and multiple myeloma (MM). Clinical trials of agents like blinatumomab, glofitamab, mosunetuzumab, and teclistamab have demonstrated deep and durable responses in heavily pretreated populations. Trispecific antibodi

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… By simultaneously engaging tumor-associated antigens and redirecting immune effector cells—most often T cells—these engineered molecules enable potent immune activation, independent of major histocompatibility complex (MHC) restriction. …

Update of early phase clinical trials in cancer immunotherapy.

Immunotherapy has revolutionized the landscape of cancer treatment and become a standard pillar of the treatment. The two main drivers, immune checkpoint inhibitors and chimeric antigen receptor T cells, contributed to this unprecedented success. However, despite the striking clinical improvements, most patients still suffer from disease progression because of the evolution of primary or acquired resistance. This mini-review summarizes new treatment options including novel targets and interesting combinational approaches to increase our understanding of the mechanisms of the action of and resi

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… Like CD4, LAG-3 binds to a major histocompatibility complex-II (MHC-II) but with much stronger affinity, prohibits the binding of the same MHC molecule to T-cell receptor (TCR) and CD4, and thus directly hinders TCR signaling in the immune response. …

Exosomes for angiogenesis induction in ischemic disorders.

Ischaemic disorders are leading causes of morbidity and mortality worldwide. While the current therapeutic approaches have improved life expectancy and quality of life, they are unable to "cure" ischemic diseases and instate regeneration of damaged tissues. Exosomes are a class of extracellular vesicles with an average size of 100-150 nm, secreted by many cell types and considered a potent factor of cells for paracrine effects. Since exosomes contain multiple bioactive components such as growth factors, molecular intermediates of different intracellular pathways, microRNAs and nucleic acids, t

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… Exosomes possess low immunogenicity as they lack the expression of major histocompatibility complex (MHC). …