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Beyond αβ T cells: NK, iNKT, and γδT cell biology in leukemic patients and potential for off-the-shelf adoptive cell therapies for AML.

Acute myeloid leukemia (AML) remains an elusive disease to treat, let alone cure, even after highly intensive therapies such as stem cell transplants. Adoptive cell therapeutic strategies based on conventional alpha beta (αβ)T cells are an active area of research in myeloid neoplasms given their remarkable success in other hematologic malignancies, particularly B-cell-derived acute lymphoid leukemia, myeloma, and lymphomas. Several limitations have hindered clinical application of adoptive cell therapies in AML including lack of leukemia-specific antigens, on-target-off-leukemic toxicity, immu

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… Positive and negative selection of the T cell repertoire: what thymocytes see (and don’t see). Nat Rev Immunol (2014) 14(6):377–91. doi: 10.1038/nri3667 10. Yates AJ. Theories and quantification of thymic selection. Front Immunol (2014) 5:13. doi: 10.3389/fimmu.2014.00013 11. …

Abstracts of the Cell Therapy Transplant Canada 2022 Annual Conference.

On behalf of Cell Therapy Transplant Canada (CTTC), we are pleased to present the Abstracts of the CTTC 2022 Annual Conference. The conference was held in-person 15-18 June 2022, in Niagara Falls, Ontario. Poster authors presented their work during a lively and engaging welcome reception on Thursday, 16 June, and oral abstract authors were featured during the oral abstract session in the afternoon on Friday, 17 June 2022. Thirty-three (33) abstracts were selected for presentation as posters and six (6) as oral presentations. The top abstracts in each of four (4) categories, (1) Basic/Translati

Paving the way towards an effective treatment for multiple sclerosis: advances in cell therapy.

Multiple sclerosis (MS) is a leading cause of chronic neurological disability in young to middle-aged adults, affecting ~2.5 million people worldwide. Currently, most therapeutics for MS are systemic immunosuppressive or immunomodulatory drugs, but these drugs are unable to halt or reverse the disease and have the potential to cause serious adverse events. Hence, there is an urgent need for the development of next-generation treatments that, alone or in combination, stop the undesired autoimmune response and contribute to the restoration of homeostasis. This review analyzes current MS treatmen

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… . | 0.3 × 10 6 cells | Antigen-specific abrogation of EAE development | LPS-treated BMDC increase the frequency of Treg (CD4+ CD25+ FoxP3+ GITR+) that are CD127+ 3G11− and inhibit those CD127 + 3G11 + Treg | | 70 Apoptotic thymocytes | C57BL/6 mice immunized with MOG 35– 55 | Splenic DC primed with …

Revving up Natural Killer Cells and Cytokine-Induced Killer Cells Against Hematological Malignancies.

Natural killer (NK) cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibitory or activating signals, such as killer immunoglobulin-like receptors, NK Group 2 member D (NKG2D), NKG2A/CD94, NKp46, and others, and recognize both foreign and self-antigens expressed by NK-susceptible targets. Recent insights into NK-cell developmental intermediates have translated into a more accurate definition of culture conditions for the in vitro generation and propagation of human NK cells

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… TG is a purified, pasteurized preparation of polyclonal γ immunoglobulin raised in rabbits against human thymocytes ( 45 ). TG expanded CIK cells more efficiently than the anti-CD3 mAb when provided to clinical-grade cultures in combination with IFN-γ and IL-2. …

Esid 2014 oral presentations.

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Posttransplant complications: molecular mechanisms and therapeutic interventions.

Posttransplantation complications pose a major challenge to the long-term survival and quality of life of organ transplant recipients. These complications encompass immune-mediated complications, infectious complications, metabolic complications, and malignancies, with each type influenced by various risk factors and pathological mechanisms. The molecular mechanisms underlying posttransplantation complications involve a complex interplay of immunological, metabolic, and oncogenic processes, including innate and adaptive immune activation, immunosuppressant side effects, and viral reactivation.

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… For instance, even at very low doses, everolimus significantly inhibits the proliferation of CD8+ T cells. 140 Cyclosporine has been demonstrated to inhibit the maturation and differentiation of thymocytes by suppressing protein kinase C activation and reducing CD4/CD8 expression levels. 141 For Teff …

Role of PARP Inhibitors in Cancer Immunotherapy: Potential Friends to Immune Activating Molecules and Foes to Immune Checkpoints.

Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) induce cytotoxic effects as single agents in tumors characterized by defective repair of DNA double-strand breaks deriving from BRCA1/2 mutations or other abnormalities in genes associated with homologous recombination. Preclinical studies have shown that PARPi-induced DNA damage may affect the tumor immune microenvironment and immune-mediated anti-tumor response through several mechanisms. In particular, increased DNA damage has been shown to induce the activation of type I interferon pathway and up-regulation of PD-L1 expression in cance

Bone marrow microenvironment in myelodysplastic neoplasms: insights into pathogenesis, biomarkers, and therapeutic targets.

Myelodysplastic neoplasms (MDS) represent a heterogeneous group of malignant hematopoietic stem and progenitor cell (HSPC) disorders characterized by cytopenia, ineffective hematopoiesis, as well as the potential to progress to acute myeloid leukemia (AML). The pathogenesis of MDS is influenced by intrinsic factors, such as genetic insults, and extrinsic factors, including altered bone marrow microenvironment (BMM) composition and architecture. BMM is reprogrammed in MDS, initially to prevent the development of the disease but eventually to provide a survival advantage to dysplastic cells. Rec

COVID-19 in patients with anemia and haematological malignancies: risk factors, clinical guidelines, and emerging therapeutic approaches.

Extensive research in countries with high sociodemographic indices (SDIs) to date has shown that coronavirus disease 2019 (COVID-19) may be directly associated with more severe outcomes among patients living with haematological disorders and malignancies (HDMs). Because individuals with moderate to severe immunodeficiency are likely to undergo persistent infections, shed virus particles for prolonged periods, and lack an inflammatory or abortive phase, this represents an overall risk of morbidity and mortality from COVID-19. In cases suffering from HDMs, further investigation is needed to achi

The IL-17 family in diseases: from bench to bedside.

The interleukin-17 (IL-17) family comprises six members (IL-17A-17F), and recently, all of its related receptors have been discovered. IL-17 was first discovered approximately 30 years ago. Members of this family have various biological functions, including driving an inflammatory cascade during infections and autoimmune diseases, as well as boosting protective immunity against various pathogens. IL-17 is a highly versatile proinflammatory cytokine necessary for vital processes including host immune defenses, tissue repair, inflammatory disease pathogenesis, and cancer progression. However, ho

Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets.

Zinc metabolism at the cellular level is critical for many biological processes in the body. A key observation is the disruption of cellular homeostasis, often coinciding with disease progression. As an essential factor in maintaining cellular equilibrium, cellular zinc has been increasingly spotlighted in the context of disease development. Extensive research suggests zinc's involvement in promoting malignancy and invasion in cancer cells, despite its low tissue concentration. This has led to a growing body of literature investigating zinc's cellular metabolism, particularly the functions of

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… ZIP8 has a substantial impact on zinc influx in effector T cells and results in reduced TCR-mediated signaling, including NF-κB and MAPK signaling, which are involved in the differentiation of T helper (Th)17 cells. 133 Similarly, mice lacking ZIP3 exhibit decreased CD4 + CD8 + double-positive (DP) thymocytes … but increased CD4 + and CD8 + single-positive thymocytes, indicating its role in regulating T cell development. 134 These findings open up new possibilities for immunotherapy to improve the prognosis by modulating the zinc transporter family genes on tumors or immune cells. …

From laboratory to clinic: opportunities and challenges of functional food active ingredients in cancer therapy.

This review provides a comprehensive analysis of the potential of functional food active ingredients in cancer prevention and therapy. It outlines the multifaceted anticancer mechanisms of bioactive compounds-such as polyphenols, carotenoids, omega-3 fatty acids, phytosterols, alkaloids, isothiocyanates, polysaccharides, phenolic acids, flavonols, and amide-bearing compounds-which include antioxidant and anti-inflammatory activities, induction of apoptosis and autophagy, modulation of the tumor microenvironment, interference with cell cycle regulation and signaling pathways, and regulation of

Genome-edited allogeneic CAR-T cells: the next generation of cancer immunotherapies.

Chimeric Antigen Receptor T (CAR-T) cell therapy has revolutionized cancer immunotherapy, particularly in hematological malignancies. However, the clinical application of autologous CAR-T cells faces significant high cost and manufacturing challenges. Universal allogeneic CAR-T cells, derived from healthy donors, represent a promising solution to these obstacles. These "off-the-shelf" therapies aim to reduce the complexity and cost of CAR-T production. Despite exciting advancements in genome-editing technologies and promising clinical trial data, significant challenges remain, including graft-

Enhancing persistence while managing cytokine release syndrome to embrace next-generation CAR-T cell therapy.

BACKGROUND: CAR-T cell therapy represents a major breakthrough in hematological malignancies. However, the trade-off between insufficient treatment persistence and treatment-related toxicities (especially cytokine release syndrome, CRS) still limits its wider clinical application. MAIN BODY: Our review aims to reframe the understanding of this central dilemma. It posits that the dynamic imbalance of intracellular signaling networks and external inflammation in the tumor microenvironment (TME) are the causes of insufficient persistence of CAR-T cells and the severe CRS. The intracellular signa

Immunosenescence, Physical Exercise, and their Implications in Tumor Immunity and Immunotherapy.

Aging is associated with a decline in immune function, termed immunosenescence, which compromises host defences and increases susceptibility to infections and cancer. Physical exercise is widely recognized for its myriad health benefits, including the potential to modulate the immune system. This review explores the bidirectional relationship between immunosenescence and physical exercise, focusing on their interplay in shaping antitumor immunity. We summarize the impact of aging on innate and adaptive immune cells, highlighting alterations that contribute to immunosenescence and cancer develo

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… Age-associated thymic atrophy impedes TCR rearrangements necessary for the production of double-positive thymocytes. The increased glycolytic activity of aging T cells can be partially attributed to variations in CD28 expression. …

Amino acid metabolism in immune cells: essential regulators of the effector functions, and promising opportunities to enhance cancer immunotherapy.

Amino acids are basic nutrients for immune cells during organ development, tissue homeostasis, and the immune response. Regarding metabolic reprogramming in the tumor microenvironment, dysregulation of amino acid consumption in immune cells is an important underlying mechanism leading to impaired anti-tumor immunity. Emerging studies have revealed that altered amino acid metabolism is tightly linked to tumor outgrowth, metastasis, and therapeutic resistance through governing the fate of various immune cells. During these processes, the concentration of free amino acids, their membrane bound tr

Pediatric Drug Development: Reviewing Challenges and Opportunities by Tracking Innovative Therapies.

The paradigm of pediatric drug development has been evolving in a "carrot-and-stick"-based tactic to address population-specific issues. However, the off-label prescription of adult medicines to pediatric patients remains a feature of clinical practice, which may compromise the age-appropriate evaluation of treatments. Therefore, the United States and the European Pediatric Formulation Initiative have recommended applying nanotechnology-based delivery systems to tackle some of these challenges, particularly applying inorganic, polymeric, and lipid-based nanoparticles. Connected with these, adv

Harnessing the potential of CAR-T cell therapy: progress, challenges, and future directions in hematological and solid tumor treatments.

Traditional cancer treatments use nonspecific drugs and monoclonal antibodies to target tumor cells. Chimeric antigen receptor (CAR)-T cell therapy, however, leverages the immune system's T-cells to recognize and attack tumor cells. T-cells are isolated from patients and modified to target tumor-associated antigens. CAR-T therapy has achieved FDA approval for treating blood cancers like B-cell acute lymphoblastic leukemia, large B-cell lymphoma, and multiple myeloma by targeting CD-19 and B-cell maturation antigens. Bi-specific chimeric antigen receptors may contribute to mitigating tumor anti

Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: children and adolescents.

The Brazilian Nutritional Consensus in Hematopoietic Stem Cell Transplantation: Children and Adolescents was developed by dietitians, physicians, and pediatric hematologists from 10 Brazilian reference centers in hematopoietic stem cell transplantation. The aim was to emphasize the importance of nutritional status and body composition during treatment, as well as the main characteristics related to patient´s nutritional assessment. This consensus is intended to improve and standardize nutrition therapy during hematopoietic stem cell transplantation. The consensus was approved by the Brazilian

Different origin-derived exosomes and their clinical advantages in cancer therapy.

Exosomes, as a class of small extracellular vesicles closely related to the biological behavior of various types of tumors, are currently attracting research attention in cancer diagnosis and treatment. Regarding cancer diagnosis, the stability of their membrane structure and their wide distribution in body fluids render exosomes promising biomarkers. It is expected that exosome-based liquid biopsy will become an important tool for tumor diagnosis in the future. For cancer treatment, exosomes, as the "golden communicators" between cells, can be designed to deliver different drugs, aiming to ac