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Tuning epigenetics to enhance cancer virotherapy.

Cancer remains a major global health challenge, driving intensive research into novel therapeutic strategies. Oncolytic viruses (OVs) including herpesviruses, adenoviruses and echoviruses, have emerged as promising agents for cancer treatment, with several achieving regulatory approval. These viruses selectively lyse tumor cells and stimulate antitumor immunity. Nevertheless, their efficacy is constrained by limitations such as neutralization by serum factors and tumor cell resistance. Concurrently, epigenetic inhibitors modulate gene expression to suppress tumor proliferation and reshape immu

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… (C) HDACis facilitate immune cell remodeling by reducing regulatory T cell (Treg)-mediated suppression, enhancing CD8 + T cell cytotoxicity via major histocompatibility complex class 1 (MHC-I) upregulation and PD-1/PD-L1 blockade, and boosting NK cell-mediated killing through granzyme and perforin release …

Targeting immunosenescence for improved tumor immunotherapy.

Tumor immunotherapy has significantly transformed the field of oncology over the past decade. An optimal tumor immunotherapy would ideally elicit robust innate and adaptive immune responses within tumor immune microenvironment (TIME). Unfortunately, immune system experiences functional decline with chronological age, a process termed "immunosenescence," which contributes to impaired immune responses against pathogens, suboptimal vaccination outcomes, and heightened vulnerability to various diseases, including cancer. In this context, we will elucidate hallmarks and molecular mechanisms underly

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… . | TLR agonists NK cells | Secreting‐cytokines (CD56 high CD16 low ) Cytotoxic (CD56 dim CD16 + ) | Decreased fraction of CD56 high NK subset, expansion of cytotoxic NK subset; Decreased cytokines production of CD56 high NK cells; Decreased lytic capacity of CD56 dim NK cells; Impaired perforin degranulation …

Bispecific antibodies in the treatment of multiple myeloma.

The treatment paradigm in myeloma is constantly changing. Upfront use of monoclonal antibodies like daratumumab along with proteasome inhibitors (PI)s, and immune modulators (IMiD)s have significantly improved survival and outcomes, but also cause unique challenges at the time of relapse. Engaging immune T cells for tumour cell kill with chimeric antigenic T-cell (CAR T-cell) therapy and bispecific antibodies have become important therapeutic options in relapsed multiple myeloma. Bispecific antibodies are dual antigen targeting constructs that engage the T cells to plasma cells through various

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… This immunological synapse causes T-cell activation and degranulation, which causes MM cell wall perforation, leading to apoptosis through perforin and granzyme B [ 10 , 11 ]. …

Systemic lupus erythematosus: pathogenesis and targeted therapy.

Systemic lupus erythematosus (SLE) is a multifaceted autoimmune disorder characterized by dysregulated immune responses and autoantibody production, which affects multiple organs and varies in clinical presentation and disease severity. The development of SLE is intricate, encompassing dysregulation within the immune system, a collapse of immunological tolerance, genetic susceptibilities to the disease, and a variety of environmental factors that can act as triggers. This review provides a comprehensive discussion of the pathogenesis and treatment strategies of SLE and focuses on the progress

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… Researches have revealed that CD8 T lymphocytes in the peripheral blood of SLE patients exhibit functional deficits, such as an impaired ability to lyse target cells and a reduction in the synthesis of granzymes and perforins [ 38 ]. …

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

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… Thus, tumor cells are guided to activated T cells, which can release preformed cytotoxic molecules such as granzyme and perforin [ 190 ]. A more detailed schematic illustration is shown in Figure 3 . …

Immunotherapy for Colorectal Cancer: Mechanisms and Predictive Biomarkers.

Though early-stage colorectal cancer has a high 5 year survival rate of 65-92% depending on the specific stage, this probability drops to 13% after the cancer metastasizes. Frontline treatments for colorectal cancer such as chemotherapy and radiation often produce dose-limiting toxicities in patients and acquired resistance in cancer cells. Additional targeted treatments are needed to improve patient outcomes and quality of life. Immunotherapy involves treatment with peptides, cells, antibodies, viruses, or small molecules to engage or train the immune system to kill cancer cells. Preclinical

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… Similar to cytotoxic CD8+ T cells, NK cells recognize and directly kill cancer cells through the release of cytotoxic granules containing perforin and granzyme or through other pathways involving FasL/Fas. NK cells also produce IFN-γ and TNF-α as well as other important anti-cancer cytokines. …

Immunotherapy in Multiple Myeloma.

Multiple myeloma is a complex disease and immune dysfunction has been known to play an important role in the disease pathogenesis, progression, and drug resistance. Recent efforts in drug development have been focused on immunotherapies to modify the MM disease process. Here, we summarize the emerging immunotherapies in the MM treatment landscape.

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… Upon the binding of FcγRs (receptors for Fc portion of immunoglobulin) to the Fc tail of the CD38-targeting antibody, NK-cells release toxic proteins including granzymes and perforins, which will kill the target cells [ 42 ]. …

Metabolic Cooperation and Competition in the Tumor Microenvironment: Implications for Therapy.

The tumor microenvironment (TME) is an ensemble of non-tumor cells comprising fibroblasts, cells of the immune system, and endothelial cells, besides various soluble secretory factors from all cellular components (including tumor cells). The TME forms a pro-tumorigenic cocoon around the tumor cells where reprogramming of the metabolism occurs in tumor and non-tumor cells that underlies the nature of interactions as well as competitions ensuring steady supply of nutrients and anapleoretic molecules for the tumor cells that fuels its growth even under hypoxic conditions. This metabolic reprogram

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… This leads to decreased mTOR activity, glycolytic capacity, interferon-γ (IFN-γ) production, and cytolytic activity via production of granzyme and perforin in T cells resulting in tumor progression ( 150 – 152 ). …

Unlocking the Potential of Ganoderma lucidum (Curtis): Botanical Overview, Therapeutic Applications, and Nanotechnological Advances.

Background:Ganoderma lucidum (GL), commonly known as the "Lingzhi" or "Reishi" mushroom, has long been recognized for its potential health benefits and medicinal properties in traditional Chinese medicine. The unique potential combination of bioactive compounds present in GL, such as triterpenoids, polysaccharides, and peptides, has inspired interest in leveraging their therapeutic potential In recent years, the emerging field of nanotechnology has opened up new possibilities for using the remarkable properties of GL at the nanoscale. Objetive: The main objective of this review is to explore t

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… . | Mice and rat models Immunomodulatory | | | In vitro In vivo | Upregulation of immunomodulators IL-12, IF-4, IL-2, IL-6, IL-4, IL-17, TNF-a, IFN-%, granulysin, perforin, and NKG2D/NCR cell surface receptors; ↑ Production of nitric oxide (NO); Activates ERK, JNK, and p38 signaling pathways. | Mice …

Cancer stem cells in personalized therapy: mechanisms, microenvironment crosstalk, and therapeutic vulnerabilities.

Cancer stem cells (CSCs) drive tumor progression, therapy resistance, and metastasis through unique membrane biology, glycosylation patterns, and metabolic adaptations. CSCs exhibit a distinct glycocalyx profile enriched in hyaluronan, heparan sulfate, and sialylated glycans, facilitating immune evasion, adhesion, and survival. Key signaling pathways-Wnt/β-catenin, Hedgehog, Notch, JAK/STAT, TGF/SMAD, and PI3K/AKT/mTOR-regulate CSC stemness and therapeutic resistance. Emerging biomarkers (CD44, CD133, ALDH1, EpCAM) and targeted therapies (CAR-T cells, miRNA modulation, lipid metabolism inhibit

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… Chimeric antigen receptor (CAR)-T cells are engineered T cells expressing an artificial receptor specific to tumor associated antigens (TAAs), which could induce the release of cytotoxic cytokines, perforin and granzyme ( Benmebarek et al., 2019 ). …

Promising Therapeutic Strategies for Hematologic Malignancies: Innovations and Potential.

In this review we explore innovative approaches in the treatment of hematologic cancers by combining various therapeutic modalities. We discuss the synergistic potential of combining inhibitors targeting different cellular pathways with immunotherapies, molecular therapies, and hormonal therapies. Examples include combining PI3K inhibitors with proteasome inhibitors, NF-κB inhibitors with immunotherapy checkpoint inhibitors, and neddylation inhibitors with therapies targeting the tumor microenvironment. Additionally, we discuss the potential use of small molecules and peptide inhibitors in hem

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… Bottom Panel : chimeric antigen receptors or CARs are genetically engineered T cells, isolated from the patient, which are modified to recognize the target surface antigens and degrade them by releasing cytokines like perforin and granzymes. …

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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… Equipped with the above modifications in the constructure, the CAR-T cells then mediated anti-tumoral effects through the perforin and granzyme, Fas and Fas-ligand interaction, as well as the release of cytokines to sensitize the cancer stroma ( Figure 2 ). 4. …

Recent Advances in Cancer Vaccines: Challenges, Achievements, and Futuristic Prospects.

Cancer is a chronic disease, and it can be lethal due to limited therapeutic options. The conventional treatment options for cancer have numerous challenges, such as a low blood circulation time as well as poor solubility of anticancer drugs. Therapeutic cancer vaccines emerged to try to improve anticancer drugs' efficiency and to deliver them to the target site. Cancer vaccines are considered a viable therapeutic technique for most solid tumors. Vaccines boost antitumor immunity by delivering tumor antigens, nucleic acids, entire cells, and peptides. Cancer vaccines are designed to induce lon

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… Furthermore, CTLs via several TCR signaling pathways, such as degranulation (release of perforin/serine protease), or via upregulation of cluster of differentiation ligand (CD95L) or TNF-related apoptosis-inducing ligand (TRAIL), induce cancer cell death. …

From monoclonals to bispecific T cell engagers: the evolving antibody-based therapy landscape in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with a poor prognosis despite advances in treatment strategies. Standard treatment regimens induce remissions in many patients, but relapse occurs in approximately half, highlighting the urgent need for novel therapeutic strategies. Antibody-based therapies have significantly improved the treatment of acute lymphoblastic leukemia (ALL), but progress in AML has been slower, with only gemtuzumab ozogamicin (GO) receiving FDA approval to date. This is largely due to the absence of AML-specific surface antigens and the challeng

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… Diagram illustrates the creation of bispecific antibodies by combining anti-CD3 and anti-TAA monoclonal antibodies to redirect T cells toward tumor cells, leading to perforin and granzyme release and tumor cell lysis. …

Exogenous Heat Shock Proteins in Oncology: Biological Roles and Clinical Implications.

Heat shock proteins (HSPs), particularly HSP70 and HSP90, are highly conserved molecular chaperones that protect cells from a wide range of stressors and maintain proteome homeostasis. In cancer, tumor cells frequently overexpress and actively release HSPs into the extracellular space and circulation in response to metabolic alterations, hypoxia, oxidative stress, and therapeutic interventions. Consequently, circulating HSP levels are often elevated in patients with malignancies compared with healthy individuals. This review summarizes current evidence on the diagnostic, prognostic, and predic

Proteoglycans as Molecular Regulators of Bone Metastasis: Extracellular Matrix Remodeling, Tumor-Bone Crosstalk, Dormancy, and Therapeutic Opportunities.

Background: Bone metastasis is a frequent and debilitating complication of advanced cancer, particularly in breast and prostate cancer, and is driven by complex interactions among tumor cells, bone-resident cells, immune populations, vascular components, and the extracellular matrix. Within this specialized microenvironment, proteoglycans have emerged as key molecular regulators of tumor-bone crosstalk, matrix remodeling, metastatic niche formation, dormancy, and therapeutic resistance. Methods: We conducted a narrative review using targeted searches of PubMed and Google Scholar for studies pu

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… . | [ 13 , 61 , 63 , 66 , 67 ] Effector lymphocytes: CD8+ T cells, Th1 cells, NK cells, and NKT cells | Perforin, granzymes, Fas/FasL, IFN-γ, NKG2D, DNAM-1; inhibited by TGF-β, PD-1/PD-L1, ROS, MDSCs, and chronic antigen exposure. | Bone resorption releases matrix-stored TGF-β, which can suppress cytotoxic …

Epigenetic modifications in early stage lung cancer: pathogenesis, biomarkers, and early diagnosis.

The integration of liquid biopsy with epigenetic markers offers significant potential for early lung cancer detection and personalized treatment. Epigenetic alterations, including DNA methylation, histone modifications, and noncoding RNA changes, often precede genetic mutations and are critical in cancer progression. In this study, we explore how liquid biopsy, combined with epigenetic markers, can provide early detection of lung cancer, potentially predicting onset up to 4 years before clinical diagnosis. We discuss the challenges of targeting epigenetic regulators, which could disrupt cellul

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… . | 233 , 243 NK cells | DNA demethylation | Active demethylation mediated by TET enzymes at NK cell effector gene loci, enhancing expression of cytotoxic molecules such as perforin and granzyme B | NK cell exosomes enhance cytotoxic responses in other NK cells by transferring demethylating enzymes and …

Novel Therapeutic Approaches in Pediatric Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, characterized by the clonal proliferation of immature lymphoid precursors. The distinction between B-cell ALL (B-ALL) and T-cell ALL (T-ALL) is fundamental, as each subtype exhibits distinct cytomorphological, genetic, and clinical features influencing prognosis and therapeutic strategies. Conventional multi-phase chemotherapy has significantly improved survival rates, yet its efficacy is limited by severe short- and long-term toxicities, highlighting the need for more selective therapeutic approaches. Advances in mole

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… After blinatumomab administration, T cells establish an immune synapse with CD19+ target cells, releasing cytolytic granules containing perforin and granzymes, and producing inflammatory cytokines such as interferon-gamma (IFN-γ), tumor necrosis factor-alpha, and interleukins (IL-2, IL-6, and IL-10) …

CAR T therapies in multiple myeloma: unleashing the future.

In recent years, the field of cancer treatment has witnessed remarkable breakthroughs that have revolutionized the landscape of care for cancer patients. While traditional pillars such as surgery, chemotherapy, and radiation therapy have long been available, a cutting-edge therapeutic approach called CAR T-cell therapy has emerged as a game-changer in treating multiple myeloma (MM). This novel treatment method complements options like autologous stem cell transplants and immunomodulatory medications, such as proteasome inhibitors, by utilizing protein complexes or anti-CD38 antibodies with pot

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… These CARs interact with tumor cells, forming an immune synapse that leads to target cell killing through various pathways, including the release of cytotoxic molecules (perforins, granzymes), induction of apoptosis via the Fas-Fas ligand molecular pathway, and cytokine production. …

Review of COVID-19 Therapeutics by Mechanism: From Discovery to Approval.

The global research and pharmaceutical community rapidly mobilized to develop treatments for coronavirus disease 2019 (COVID-19). Existing treatments have been repurposed and new drugs have emerged. Here we summarize mechanisms and clinical trials of COVID-19 therapeutics approved or in development. Two reviewers, working independently, reviewed published data for approved COVID-19 vaccines and drugs, as well as developmental pipelines, using databases from the following organizations: United States Food and Drug Administration (US-FDA), European Medicines Agency (EMA), Japanese Pharmaceutical

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… Recognition of IMM-101 by dendritic cells can enhance antigen processing and presentation capacity, increase expression of co-stimulatory molecules, and promote secretion of anti-viral interferon-γ, perforin, and granzyme B. 102 IMM-101 is currently being developed as a drug for treating pancreatic cancer …