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Limited Clinical Efficacy with Potential Adverse Events in a Pilot Study of Autologous Adoptive Cell Therapy in Canine Oral Malignant Melanoma.

Adoptive cell therapy (ACT) has been studied in several human and canine cancers with some promising clinical outcomes but not in canine oral malignant melanoma (OMM). Our manuscript aimed to explore one kind of ACT, the ex vivo-expanded autologous immune cell infusion in canine OMM, as this tumor remains a treatment dilemma. The study recruited dogs with histopathological diagnoses of oral malignant melanoma, generated their peripheral blood mononuclear cells, expanded them into predominantly non-B non-T cells via stimulations of IL-15, IL-2, and IL-21, and then re-infused the cells into tumo

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… Tumor cells may down-regulate their major histocompatibility complex (MHC) expression to evade recognition and elimination by T cells, whereas NK cells can attack those tumor cells with abnormal MHC expression, making them a potent candidate for ACT with a lower risk of graft-versus-host adverse events …

Cancer risks in rheumatoid arthritis patients who received immunosuppressive therapies: Will immunosuppressants work?

BACKGROUND: Exploring the cancer risks of rheumatoid arthritis (RA) patients with disease-modifying anti-rheumatic drugs (DMARDs) can help detect, evaluate, and treat malignancies at an early stage for these patients. Thus, a comprehensive analysis was conducted to determine the cancer risk of RA patients using different types of DMARDs and analyze their relationship with tumor mutational burdens (TMBs) reflecting immunogenicity. METHODS: A thorough search of PubMed, EMBASE, Web of Science, and Medline was conducted up to 20 August 2022. Standardized incidence ratios (SIRs) were constructed w

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… TMB refers to the number of somatic mutations after the tumor genome removes the germline mutation; a large number of mutated somatic cells will produce a large number of altered peptides, some of which are successfully expressed and processed by the major histocompatibility complex, thereby producing …

Иммунометаболизм в старении мозга и нейродегенерации: преодоление метаболических путей и иммунные ответные меры.

Сложный набор взаимодействий между иммунной системой и метаболизмом, известный как иммунометаболизм, стал критическим регулятором последствий заболеваний в центральной нервной системе. В ходе многочисленных исследований метаболические расстройства увязывались с ослабленной иммунной реакцией при старении мозга, нейродегенеративных расстройствах и травме мозга. В этом обзоре мы обсудим вопрос о том, как нарушения баланса иммунометаболизма мозга способствуют патофизиологии дисфункции мозга. В первой части обзора резюмируется вклад таких критических групп иммунной клетки, как микроглии, астроциты,

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… The increased expression of inhibitory molecules, alterations in cell major histocompatibility complex (MHC), and reduced cell cytotoxicity seen in aging can dysregulate immunosurveillance and clearance, leading to the accumulation of senescent cells [ 18 ]. …

Gene and Cell Therapy for Sarcomas: A Review.

Background: The heterogeneity of sarcomas and resulting distinct sub-type specific characteristics, their high recurrence rates, and tendency for distant metastasis, continue to present significant challenges to providing optimal treatments. Objective: To provide a comprehensive review of current literature and clinical trials in gene and cell therapies for sarcomas. Methods: A comprehensive literature search was conducted utilizing the following databases: PubMed, Medline, Google Scholar and clinicaltrials.gov. Search terms included "gene therapy", "cell therapy", "NK cell therapy, "CAR-T the

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… These cells possess a unique array of activating and inhibitory receptors on their cell surface, enabling them to recognize viral proteins, stress-induced ligands, and decreased Major Histocompatibility Complex (MHC) class I-expressing molecules. …

Chronic stress: a fourth etiology in tumorigenesis?

Chronic stress, driven by persistent psychological, environmental, or physiological factors, is a prolonged heightened state of stress response that disrupts homeostasis. When unmanaged, it will lead to sustained negative emotions such as depression, loneliness, anxiety, and emotional adversity. This persistent emotional distress not only exacerbates mental health disorders but also poses significant risks to physical health. Increasing evidence suggests a strong link between chronic stress, stress-related hormones, and the rising incidence of malignancies. As a result, chronic stress might be

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… Chronic stress via adrenergic hormones also inactivates the STAT1-interferon regulatory factor (IRF)-1 pathway, leading to the simultaneous suppression of major histocompatibility complex (MHC)-I and upregulate the programmed cell death ligand-1 (PD-L1) expressions reducing T cell surveillance [ 150 … histocompatibility complex Matrix metalloproteinases Medial prefrontal cortex Mitochondrial reactive oxygen species Mammalian target of rapamycin Nicotinamide adenine dinucleotide phosphate Nuclear factor kappa-light-chain-enhancer of activated B cells Nerve growth factor Nuclear respiratory …

The "Magic Bullet" Is Here? Cell-Based Immunotherapies for Hematological Malignancies in the Twilight of the Chemotherapy Era.

Despite the introduction of a plethora of different anti-neoplastic approaches including standard chemotherapy, molecularly targeted small-molecule inhibitors, monoclonal antibodies, and finally hematopoietic stem cell transplantation (HSCT), there is still a need for novel therapeutic options with the potential to cure hematological malignancies. Although nowadays HSCT already offers a curative effect, its implementation is largely limited by the age and frailty of the patient. Moreover, its efficacy in combating the malignancy with graft-versus-tumor effect frequently coexists with undesirab

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… Defects in antigen processing and presentation frequently arise as a result of a loss-of-function mutation in β2-microglobulin and downregulation of major histocompatibility complex (MHC) class I molecules, which prevent T cell activation and cytotoxic activity [ 32 ]. …

The innate defenders: a review of natural killer cell immunotherapies in cancer.

Cancer is a condition that has been with us for centuries; however, the therapies that have been developed are often associated with significant toxicity and various side effects. Recent advances in immunology have revealed the potential of the immune system to fight cancer, leading to the emergence of immunotherapy. This review focuses on Natural Killer (NK) cells, innate immune effectors with a remarkable ability to directly kill cancer cells. We will explore the historical context of cancer treatment, the nature of NK cells, and the ways they have been developed to enhance their anti-tumor

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… Inhibitory signals NK cells also possess inhibitory receptors that recognize self-major histocompatibility complex class I (MHC-I) molecules on healthy cells. This “missing-self” recognition prevents NK cells from attacking healthy tissues. …

Cardiovascular toxicities associated with chimeric antigen receptor T-cell therapy.

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a groundbreaking immunotherapeutic approach, particularly for oncohematological patients who are refractory to conventional treatments. As clinical trials expand the applications of CAR T-cell therapy beyond hematologic malignancies, a critical understanding of its associated toxicities, particularly cardiovascular complications, becomes imperative. This review synthesizes current literature on the interplay between cytokine release syndrome (CRS) and cardiotoxicity related to CAR T-cell therapy, emphasizing the potential severity o

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… Normal T cells trigger an immune response when they recognize antigens presented to them by antigen-presenting cells (APCs) that are coupled to major histocompatibility complex (MHC) molecules. Cancer cells can also express MHC molecules on their surface membranes ( Darragh and Karam, 2022 ). …

TP53-mutated myelodysplastic syndromes and acute myeloid leukemia: a comprehensive overview of targeted approaches.

TP53-mutated acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) represent a biologically and clinically distinct subset of myeloid malignancies characterized by poor prognosis, resistance to standard therapies, and high rates of relapse. TP53 mutations, particularly biallelic are frequently associated with complex karyotypes and confer profound chemoresistance. Although hypomethylating agents and venetoclax-based combinations provide modest benefit, durable remissions remain rare. Novel therapeutic strategies targeting mutant p53, restoring wild-type function, or exploiting synth

Therapeutic Targeting of DNA Damage Repair in the Era of Precision Oncology and Immune Checkpoint Inhibitors.

Cancer manifestation is a multistep process involving accumulation of various genetic and epigenetic changes that results in oncogenic "hallmarks of cancer" processes including genomic instability. Exploitation of aberrant DNA-damage response (DDR) mechanisms in cancer is in part a goal of many therapeutic strategies, and recent evidence supports the role of targeting DDR in modulating the tumor immune microenvironment to enhance immunotherapeutic response. Improved cancer profiling, including next-generation and whole-genome mutational sequencing of tumor tissue, as well as circulating nuclei

Воздействие иммунотерапии рака на рождаемость: уделение особого внимания гематологическим заболеваниям.

В последние годы лечению раковых заболеваний способствовали новые эффективные методы лечения, включая иммунную терапию. Хотя эта терапия повышает показатели выживаемости рака, она может изменять иммунную реакцию и вызывать долгосрочные побочные эффекты, гонадотоксичные последствия и потенциальное воздействие на фертильность мужчин и женщин вызывают все большую озабоченность. Иммунотерапии, такие, как ингибиторы иммунной системы, иммуномодуляторы, моноклонные антитела и CAR-T, могут привести к повышению уровней проинфламмации цитокинов и связанных с иммунным иммунитетом неблагоприятных явлений,

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… Major Histocompatibility Complex (MHC) molecules, particularly Human Leukocyte Antigen (HLA), are crucial for successful pregnancy [ 23 , 24 ]. …

Emerging treatment options for patients with p53-pathway-deficient CLL.

Over the past 40 years, p53 has been the most widely studied protein in cancer biology. Originally thought to be an oncogene due to its stabilization in many cancers, it is now considered to be one of the most critical tumor suppressors in a cell's ability to combat neoplastic transformation. Due to its critical roles in apoptosis, cell-cycle arrest, and senescence, TP53 deletions and mutations are commonly observed and are often a portent of treatment failures and poor clinical outcomes. This is particularly true in chronic lymphocytic leukemia (CLL), as patients with p53 alterations have his

Molecularly Targeted Therapies in Oncology: Mechanisms, Resistance, and Combination Strategies.

Targeted therapies are reshaping oncology by enabling treatment selection based on actionable molecular alterations, improving precision, and reducing unnecessary toxicity. This review provides an up-to-date overview of current targeted treatment modalities and the medicinal chemistry principles that support their discovery and optimization. We synthesize evidence on small-molecule and biologic strategies spanning receptor and non-receptor kinases and their major signaling axes (PI3K-AKT-mTOR and RAS-RAF-MEK-ERK), apoptosis regulation (BCL-2 family), DNA repair via poly(ADP-ribose) polymerase

Emerging Targets in Non-Small Cell Lung Cancer.

Lung cancer is responsible for a high burden of disease globally. Over the last two decades, the discovery of targetable oncogenic genomic alterations has revolutionized the treatment landscape for early-stage and advanced non-small cell lung cancer (NSCLC). New molecular drivers continue to emerge as promising therapeutic targets, including KRAS non-G12C, RAF/MEK, HER3, Nectin-4, folate receptor alpha, ITGB6, and PRMT5. In this review, we summarize the emerging molecular targets with a potential clinical impact in advanced NSCLC, elaborating on their clinical characteristics and specific mech

Student Summer Research Awards - SSRAAbstracts of the SSRA September 2022 meeting, UCD School of Medicine.

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Cardiotoxicity of anti-cancer drugs: cellular mechanisms and clinical implications.

Cardio-oncology is an emerging field that seeks to enhance quality of life and longevity of cancer survivors. It is pertinent for clinicians to understand the cellular mechanisms of prescribed therapies, as this contributes to robust understanding of complex treatments and off-target effects, improved communication with patients, and guides long term care with the goal to minimise or prevent cardiovascular complications. Our aim is to review the cellular mechanisms of cardiotoxicity involved in commonly used anti-cancer treatments and identify gaps in literature and strategies to mitigate card

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… T-cell activation is initiated by foreign peptides showcased on APCs coupled with the major histocompatibility complex (MHC). The co-stimulatory signal is conveyed through the APC ligand CD80, which triggers cell activation and subsequent proliferation. …

Nanoparticle Strategies for Bone Metastasis Immunotherapy: Targeting, Immune Reprogramming and Combination Therapy.

Bone metastases remain one of the most clinically devastating complications of advanced cancer, particularly in breast, prostate, and lung malignancies, where they drive pain, fractures, hypercalcemia, and progressive functional decline. Their management is further complicated by a highly immunosuppressive bone microenvironment characterized by osteoclast-driven bone destruction, myeloid cell dominance, impaired antigen presentation, and weak effector T-cell infiltration, all of which limit the activity of conventional immunotherapies. In this setting, nanoparticles are emerging not merely as

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… Upon loading with PTT-generated antigens, dendritic cells activate CD8 + cytotoxic T-cells in lymph nodes and augment MHC (Major Histocompatibility Complex Class I) I antigen presentation, particularly when combined with checkpoint blockade or mTOR inhibition [ 141 , 142 ]. …

Tumor heterogeneity as a driver of drug resistance and its implications for personalized therapy.

Tumors are highly dynamic diseases characterized by significant heterogeneity. They consist of multiple cellular populations with distinct properties that respond differently to therapeutic pressure. This heterogeneity may arise from spatial variation across tumor regions (spatial heterogeneity) as well as from temporal changes during tumor evolution and treatment (temporal heterogeneity). As a consequence, drug-resistant subclones often emerge under therapy and contribute to treatment failure. Advances in single-cell and spatial multi-omics technologies enable precise quantification of tumor

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… The authors identified an immune-resistant tumor-cell state characterized by high expression of cell cycle and transcription factor genes [cyclin-dependent kinase (CDK) 4/6–E2F–MYC axis], low expression of IFN-γ-response and major histocompatibility complex class I (MHC-I) pathways, a blunted response …

New hopes and challenges in targeted therapy and immunotherapy for primary central nervous system lymphoma.

Primary central nervous system lymphoma (PCNSL) is non-Hodgkin's lymphoma (NHL) confined to the central nervous system. Most of the patients eventually develop relapsed/refractory (R/R) PCNSL, and the overall prognosis for PCNSL remains dismal. Recently, gene sequencing, transcriptome sequencing, and single-cell sequencing platforms have provided a large amount of data revealing the mechanisms underlying the pathogenesis and drug resistance in PCNSL, including the activation of the NF-κB signaling pathway in tumor cells, tumor heterogeneity, and the immunosuppressive tumor microenvironment. Ad

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… BiTEs link T cells and tumors, triggering cell death by target cell lysis without conventional major histocompatibility complex (MHC) class I/peptide antigen recognition ( 82 ). …

Targeted CD7 CAR T-cells for treatment of T-Lymphocyte leukemia and lymphoma and acute myeloid leukemia: recent advances.

The high expression of CD7 targets in T-cell acute lymphoblastic leukemia (T-ALL) and T-lymphoma has attracted considerable attention from researchers. However, because CD7 chimeric antigen receptor (CAR) T-cells undergo fratricide, CD7 CAR T-cells develop an exhaustion phenotype that impairs the effect of CAR T-cells. There have been significant breakthroughs in CD7-targeted CAR T-cell therapy in the past few years. The advent of gene editing, protein blockers, and other approaches has effectively overcome the adverse effects of conventional methods of CD7 CAR T-cells. This review, in conjunc

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… Unlike major histocompatibility complex (MHC)-dependent T-cell receptors (TCRs), CAR can recognize antigens from any MHC background, allowing CAR T cells to target tumor cells that achieve immune evasion through down regulation of MHC expression or impaired proteasome antigen processing ( 2 , 3 ). …