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COVID-19 signalome: Pathways for SARS-CoV-2 infection and impact on COVID-19 associated comorbidity.

The COVID-19 pandemic has been the focus of research the past two years. The major breakthrough was made by discovering pathways related to SARS-CoV-2 infection through cellular interaction by angiotensin-converting enzyme (ACE2) and cytokine storm. The presence of ACE2 in lungs, intestines, cardiovascular tissues, brain, kidneys, liver, and eyes shows that SARS-CoV-2 may have targeted these organs to further activate intracellular signalling pathways that lead to cytokine release syndrome. It has also been reported that SARS-CoV-2 can hijack coatomer protein-I (COPI) for S protein retrograde

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… However, when concentrations of T helper (Th)17 cells, perforins, and granulysin-expressing cluster of differentiation 8 T-cell (CD8 T) cells are enhanced, it will contribute to hyperinflammation. Moreover, host Th17 responses are major contributors to cytokine storms [ 43 ]. …

Role of Protein Kinase CK2 in Aberrant Lipid Metabolism in Cancer.

Uncontrolled proliferation is a feature defining cancer and it is linked to the ability of cancer cells to effectively adapt their metabolic needs in response to a harsh tumor environment. Metabolic reprogramming is considered a hallmark of cancer and includes increased glucose uptake and processing, and increased glutamine utilization, but also the deregulation of lipid and cholesterol-associated signal transduction, as highlighted in recent years. In the first part of the review, we will i) provide an overview of the major types of lipids found in eukaryotic cells and their importance as med

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… Extending the C2 domain family: C2s in PKCs delta, epsilon, eta, theta, phospholipases, GAPs, and perforin. Protein Sci. 1996;5:162–166. doi: 10.1002/pro.5560050120. 26. Eyster K.M. …

Наномедицина - мощная терапия CAR-T для множественной миеломы: к программируемой, долговременной и точной иммунотерапии.

Множественная миелома (ММ) по-прежнему является трудновыполнимой гематологией. Несмотря на то, что терапия против созревания клеток B (BCMA), ориентированная на химерик антигенный рецептор Т-клектор (CAR-T), существенно углубила клиническую реакцию у пациентов с рецидивом/переносом MM, ее более широкое клиническое применение по-прежнему сдерживается рецидивом после лечения, недостаточной устойчивостью реакции, длительными сроками производства и ограниченной доступностью. Растущие данные свидетельствуют о том, что рецидив после лечения CAR-T в MM происходит не из одного механизма, а из конверге

Иммуномодулирующий и противовоспалительный потенциал S-нитросглутатиона (GSNO) при множественной склерозе: обзор механизмов и терапевтических перспектив.

Многофакторная демиелинизация (МС) — это хроническое аутоиммунное заболевание центральной нервной системы (СНС), характеризующееся длительной нейроинфляминацией, окислительным стрессом, демиелинизацией и прогрессирующей нейродегенерацией. Несмотря на то, что МС остается неизлечимым, современные терапевтические средства (ТМС) помогают снизить частоту обострений и задерживать прогрессирование заболевания. Недавно разработанные инъекционные и инфузийные биологические ТМС обеспечивают целенаправленную иммуномодуляцию, но их клиническая полезность ограничена родственными методами введения и возможн

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… They are abundant in active MS lesions and directly damage oligodendrocytes and neurons through perforin- and granzyme-mediated cytotoxicity, as well as amplify CNS inflammation by producing IFN-γ and TNF-α ( 189 ). … In contrast, CD56 dim NK cells represent the major circulating NK-cell population and exhibit potent cytotoxic activity through perforin- and granzyme-mediated killing ( 198 ). …

Natural killer cells, macrophages and dendritic cells as innate immune therapies for blood cancers.

Innate immune cells are emerging as powerful allies in the fight against blood cancers. Natural Killer (NK) cells, macrophages, and dendritic cells (DCs)—once viewed mainly as supporting players—are now at the forefront of next-generation immunotherapies, owing to their rapid, antigen-independent tumor recognition and potent effector functions. This review highlights their distinct anti-tumor roles: NK cells’ cytotoxicity and “missing-self” recognition, the dual and adaptable nature of macrophages in the tumor microenvironment (TME), and the antigen-presenting capabilities of DCs that bridge i

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… Upon engagement with target cells, NK cells unleash their cytotoxic potential by releasing granules containing perforin and granzymes, which induce target cell death [ 12 , 14 ]. An important mechanism of NK cell-mediated anti-tumor activity is the “missing self” recognition mechanism. …

Cancer immunotherapy insights: key takeaways from the ADSCC bone marrow and cellular therapy congress 2024.

The rising global cancer burden underscores the urgent need for innovative and effective therapies. Molecular and cellular immunology advances have revolutionized cancer immunotherapy, transforming laboratory discoveries into clinical breakthroughs. The Second Bone Marrow Transplant and Cellular Therapy Congress, held in Abu Dhabi, United Arab Emirates (UAE), on October 26th - 27th, 2024, and sponsored by the Abu Dhabi Stem Cells Center (ADSCC), convened global experts to discuss cutting-edge developments in adoptive cell transfer (ACT); chimeric antigen receptor T-cell (CAR-T) therapy, tumor-

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… Additionally, CD8 + TILs from responders exhibited increased cytotoxicity, exhaustion, and co-stimulatory signaling, characterized by upregulation of effector molecules (including granzyme B and perforin) and enhanced co-stimulatory pathways such as CD28-associated signaling, together with increased …

Breaking Boundaries: Immunotherapy for Myeloid Malignancies.

Immunotherapy has revolutionized the treatment of myeloid oncologic diseases, particularly for patients resistant to chemotherapy or ineligible for allogeneic stem cell transplantation due to age or fitness constraints. As our understanding of the immunopathogenesis of myeloid malignancies expands, so too do the treatment options available to patients. Immunotherapy in myeloid malignancies, however, faces numerous challenges due to the dynamic nature of the disease, immune dysregulation, and the development of immune evasion mechanisms. This review outlines the progress made in the field of im

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… NK cells eliminate target cells via the production of perforin and granzyme B, a direct cellular killing mechanism. Additionally, they utilize the indirect means of ADCC. …

Immune checkpoints represent a promising breakthrough in targeted therapy and prognosis of myelodysplastic syndrome.

Myelodysplastic syndrome (MDS) is a hematological malignancy of undetermined etiology, possibly linked to chromosomal structural alterations, genetic mutations, presentation and carcinogenicity of variant antigens on cell surface, and the generation of pro-inflammatory microenvironment in the bone marrow. Current drugs are unable to cure this disease, and therefore, decreasing the survival and proliferation of malignant cells to delay disease progression and extend the survival time of patients becomes the primary approach to management. In recent years, the immune system has received increasi

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… Increased CD8+CD27+perforin+ T cells and decreased CD8+CD70+ T cells may be immune biomarkers for aplastic anemia severity. Blood cells mol dis. 2019;77:34–42. doi: 10.1016/j.bcmd.2019.03.009. 88. …

Management and Prevention of Cellular-Therapy-Related Toxicity: Early and Late Complications.

Chimeric Antigen Receptor T (CAR-T) cell therapy has dramatically changed prognosis and treatment of relapsed and refractory hematologic malignancies. Currently the 6 FDA approved products target various surface antigens. While CAR-T therapy achieves good response, life-threatening toxicities have been reported. Mechanistically, can be divided into two categories: (1) toxicities related to T-cell activation and release of high levels of cytokines: or (2) toxicities resulting from interaction between CAR and CAR targeted antigen expressed on non-malignant cells (i.e., on-target, off-tumor effec

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… Perforin-deficient CAR T cells recapitulate late-onset inflammatory toxicities observed in patients. J. Clin. Investig. 2020;130:5425–5443. doi: 10.1172/JCI130059. 64. Holtzman N.G., Xie H., Bentzen S., Kesari V., Bukhari A., El Chaer F., Lutfi F., Siglin J., Hutnick E., Gahres N., et al. …

Multiple Myeloma Cell-Derived Exosomes: Implications on Tumorigenesis, Diagnosis, Prognosis and Therapeutic Strategies.

Multiple myeloma (MM) is a hematological disease that is still not curable. The bone marrow milieu, with cellular and non-cellular elements, participate in the creation of a pro-tumoral environment enhancing growth and survival of MM plasma cells. Exosomes are vesicles oscillating in dimension between 50 nm and 100 nm in size that can be released by various cells and contribute to the pathogenesis and progression of MM. Exosomes enclose proteins, cytokines, lipids, microRNAs, long noncoding RNAs, and circular RNAs able to regulate interactions between MM plasma cells and adjacent cells. Throug

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… They support programmed cell death and block growth of HD-CD4+ T, block perforin of HD-CD8+ T, reduce programmed cell death and stimulate growth of HD-Treg, and decrease TGF-β delivery of MM-Treg [ 50 ]. …

T-Regulatory Cells In Tumor Progression And Therapy.

Regulatory T cells (Tregs) are important members of the immune system regulating the host responses to infection and neoplasms. Tregs prevent autoimmune disorders by protecting the host-cells from an immune response, related to the peripheral tolerance. However, tumor cells use Tregs as a shield to protect themselves against anti-tumor immune response. Thus, Tregs are a hurdle in achieving the complete potential of anti-cancer therapies including immunotherapy. This has prompted the development of novel adjuvant therapies that obviate their negative effects thereby enhancing the therapeutic ef

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… n-Tregs are mainly formed in thymus and need costimulatory molecules for their development and lineage commitment. 18 n-Tregs suppress immune effector lymphocytes like T helper cells (Th cells), Th1, Th2, Th17 and follicular Th cells (Tfh cells) in a contact-dependent manner that requires Granzymes B/perforin …

Oral complications in hematopoietic stem cell recipients: the role of inflammation.

Hematopoietic stem cell transplantation (HSCT) is widely used as a potentially curative treatment for patients with various hematological malignancies, bone marrow failure syndromes, and congenital immune deficiencies. The prevalence of oral complications in both autologous and allogeneic HSCT recipients remains high, despite advances in transplant medicine and in supportive care. Frequently encountered oral complications include mucositis, infections, oral dryness, taste changes, and graft versus host disease in allogeneic HSCT. Oral complications are associated with substantial morbidity and

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… Both Fas/FasL-dependent and perforin/granzyme-dependent apoptosis are important in GvHD-induced tissue damage [ 74 ]. Traditionally, aGvHD is considered to be driven by Th1 cytokines and mediated by CD8+ effectors [ 70 ]. …

Application and mechanistic research of novel therapeutic strategies in cisplatin-resistant small cell lung cancer.

IntroductionSmall cell lung cancer (SCLC) initially responds well to cisplatin-based chemotherapy, but rapid development of drug resistance limits long-term efficacy and subsequent treatment options. Understanding the multifactorial mechanisms of cisplatin resistance is essential for improving patient outcomes. This review synthesizes recent preclinical and clinical advances, focusing on seven key resistance mechanisms and emerging therapeutic strategies, including immunotherapy, targeted therapy, and novel chemotherapeutic agents.DiscussionCisplatin resistance in SCLC arises through multiple

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… PFN, perforin; GzmB, GranzymeB; INEγ, Interferon γ; INEα, Interferon α Mechanisms of cisplatin resistance Mechanisms of drug deposition reduction leading to resistance Studies have suggested that the drug efflux pumps of SCLC cells are greatly associated with their resistance feature to cisplatin-based …

Advancing Immunotherapy in Chronic Lymphocytic Leukemia.

The treatment of chronic lymphocytic leukemia (CLL) has significantly shifted from chemoimmunotherapy to targeted therapies like Bruton's tyrosine kinase and BCL2 inhibitors. Despite these advancements, CLL remains an incurable disease characterized by immune dysregulation, therapeutic resistance, and cumulative toxicities. To overcome these challenges, novel immunotherapeutic strategies are emerging as fundamentally different approaches that target immune-tumor interactions. These innovations include novel monoclonal antibodies, bispecific antibodies that redirect T cell cytotoxicity, chimeri

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… This crosslinking activates T lymphocytes, resulting in the secretion of perforin and granzyme B, which induce apoptosis in the targeted leukemia cells [ 74 ]. To date, the strongest evidence for the efficacy and safety of BsAbs in CLL treatment comes from epcoritamab clinical trials. …

От генов к окружающей среде: жизненный подход к профилактике педиатрических аутоиммунных заболеваний.

Аутоиммунные заболевания у детей, включая тип 1 Все более серьезной проблемой для здоровья людей во всем мире являются диабет, болезни селиака и детский артрит. Этот всплеск, слишком быстрый для того, чтобы его можно было объяснить только генетическими изменениями, подчеркивает важнейшую роль экологических факторов и подчеркивает настоятельную необходимость принятия активных превентивных мер. Этот обзор представляет собой комплексную, основанную на фактических данных основу для профилактики педиатрических аутоиммунных заболеваний по всему спектру услуг, начиная с первичной и заканчивая третичн

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… On the left, an active autoimmune attack is shown, characterized by autoreactive CD8⁺ cytotoxic T cells infiltrating the pancreatic islet and inducing β-cell destruction through perforin- and granzyme-mediated cytotoxicity, accompanied by pro-inflammatory cytokine release ( e.g. , interleukin-2, interferon-gamma …

A systematic review of the last two decades of NK cell-based clinical trials: state of the art of AML therapy.

BACKGROUND: Acute myeloid leukemia (AML) remains a significant challenge in hematologic oncology, with high relapse rates and limited treatment options. Natural killer (NK) cells, as key effectors of innate immunity, have shown strong anti-leukemic activity, making them promising candidates for immunotherapy. Despite increasing clinical interest, a comprehensive evaluation of NK cell-based therapies in AML is still needed. METHODS: This systematic review follows the PRISMA guidelines to analyze clinical trials evaluating NK cell therapy in AML, either as a standalone treatment or in combinatio

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… The NK cells also exhibited prominent activation and proliferation features, characterized by elevated levels of granzyme B and perforin [ 85 , 86 ]. …

Role of T cells and cytokines in the pathogenesis of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a long-term autoimmune disease. It causes persistent joint inflammation, aberrant tissue growth, and progressive joint deterioration. T cells have a key role in the onset of RA. They identify and trigger other immune cells, and produce inflammatory signals such as interleukin-6 (IL-6), interleukin-17 (IL-17), and tumor necrosis factor-α (TNF-α). Prolonged inflammation and tissue damage are caused by an imbalance between regulatory T cells (Tregs) and pro-inflammatory T helper 17 (Th17) cells. Additionally, the condition is exacerbated by uncontrolled cytokine netwo

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… Upon binding BCMA on malignant plasma cells, cilta-cel activates T cells, leading to cytokine release and cytotoxic lysis via perforin–granzyme and Fas–FasL pathways. …

Immune mediated support of metastasis: Implication for bone invasion.

Bone is a common organ affected by metastasis in various advanced cancers, including lung, breast, prostate, colorectal, and melanoma. Once a patient is diagnosed with bone metastasis, the patient's quality of life and overall survival are significantly reduced owing to a wide range of morbidities and the increasing difficulty of treatment. Many studies have shown that bone metastasis is closely related to bone microenvironment, especially bone immune microenvironment. However, the effects of various immune cells in the bone microenvironment on bone metastasis remain unclear. Here, we describe

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… CD8 + T cells, also known as cytotoxic T lymphocytes (CTLs), have cytotoxic potential through the production of perforin, granzyme, and IFN‐γ [ 176 ]. …

Bispecific Antibodies in Hematological Malignancies: A Scoping Review.

Bispecific T-cell engagers (BiTEs) and bispecific antibodies (BiAbs) have revolutionized the treatment landscape of hematological malignancies. By directing T cells towards specific tumor antigens, BiTEs and BiAbs facilitate the T-cell-mediated lysis of neoplastic cells. The success of blinatumomab, a CD19xCD3 BiTE, in acute lymphoblastic leukemia spearheaded the expansive development of BiTEs/BiAbs in the context of hematological neoplasms. Nearly a decade later, numerous BiTEs/BiAbs targeting a range of tumor-associated antigens have transpired in the treatment of multiple myeloma, non-Hodgk

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… Activated T cells release perforin and granzyme, resulting in the T-cell-dependent killing of tumor cells via apoptosis. …

Retrospective analysis of the preparation and application of immunotherapy in cancer treatment (Review).

Monoclonal antibody technology plays a vital role in biomedical and immunotherapy, which greatly promotes the study of the structure and function of genes and proteins. To date, monoclonal antibodies have gone through four stages: murine monoclonal antibody, chimeric monoclonal antibody, humanised monoclonal antibody and fully human monoclonal antibody; thousands of monoclonal antibodies have been used in the fields of biology and medicine, playing a special role in the pathogenesis, diagnosis and treatment of disease. In this review, we compare the advantages and disadvantages of hybridoma te

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… NK cells activated by antibodies can release cellular cytotoxic granules (perforin and granzyme) to achieve cell apoptosis on the one hand, while they can release cytokines and chemokines to inhibit cell proliferation and angiogenesis on the other ( 128 ). …