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Assessment of circulating proteins in thyroid cancer: Proteome-wide Mendelian randomization and colocalization analysis.

The causality between circulating proteins and thyroid cancer (TC) remains unclear. We employed five large-scale circulating proteomic genome-wide association studies (GWASs) with up to 100,000 participants and a TC meta-GWAS (nCase = 3,418, nControl = 292,703) to conduct proteome-wide Mendelian randomization (MR) and Bayesian colocalization analysis. Protein and gene expressions were validated in thyroid tissue. Through MR analysis, we identified 26 circulating proteins with a putative causal relationship with TCs, among which NANS protein passed multiple corrections (P BH = 3.28e-5, 0.05/1,5

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… Inclusion criteria for cis-pQTLs in the analysis were as follows: (1) genome-wide significant association threshold ( P < 5e-8); (2) loci within the major histocompatibility complex (MHC) region on chromosome 6 (26-34MB) were excluded due to their complex LD patterns; (3) only independent loci were considered …

Pediatric Acute Lymphoblastic Leukemia Emerging Therapies-From Pathway to Target.

Over the past 40 years, the 5-years-overall survival rate of pediatric cancer reached 75-80%, and for acute lymphoblastic leukemia (ALL), exceeded 90%. Leukemia continues to be a major cause of mortality and morbidity for specific patient populations, including infants, adolescents, and patients with high-risk genetic abnormalities. The future of leukemia treatment needs to count better on molecular therapies as well as immune and cellular therapy. Advances in the scientific interface have led naturally to advances in the treatment of childhood cancer. These discoveries have involved the recog

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… CAR T-cells employ a strategy independent of human leukocyte antigen, being modified to produce chimeric antigen receptors directed against a particular tumor surface antigen; as a result, they are both antigen-specific and major histocompatibility complex (MHC)-independent [ 109 ]. …

Exploring the dual role of B cells in solid tumors: implications for head and neck squamous cell carcinoma.

In the tumor milieu of head and neck squamous cell carcinoma (HNSCC), distinct B cell subpopulations are present, which exert either pro- or anti-tumor activities. Multiple factors, including hypoxia, cytokines, interactions with tumor cells, and other immune infiltrating lymphocytes (TILs), alter the equilibrium between the dual roles of B cells leading to cancerogenesis. Certain B cell subsets in the tumor microenvironment (TME) exhibit immunosuppressive function. These cells are known as regulatory B (Breg) cells. Breg cells suppress immune responses by secreting a series of immunosuppressi

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… Meanwhile, the antigen-presenting B cells present antigens to effector T cells via major histocompatibility complex (MHC) molecules at the cell surface, which also aid in the anti-tumor immunity. … TIL-B cells, tumor-infiltrating B cells; GC B cell, germinal center B cell; DC, dendritic cell, T FH cell, follicular helper T cell; MHC, major histocompatibility complex; AID, activation-induced deaminase; GrB, granzyme B; Treg cell, regulatory T cell; MDSC, myeloid-derived suppressor cell; hi, high …

CAR-T Cell Therapy in the Treatment of Pediatric Non-Hodgkin Lymphoma.

Non-Hodgkin lymphomas (NHL) are a group of cancers that originate in the lymphatic system, especially from progenitor or mature B-cells, T-cells, or natural killer (NK) cells. NHL is the most common hematological malignancy worldwide and also the fourth most frequent type of cancer among pediatric patients. This cancer can occur in children of any age, but it is quite rare under the age of 5 years. In recent decades, available medicines and therapies have significantly improved the prognosis of patients with this cancer. However, some cases of NHL are treatment resistant. For this reason, immu

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… In CAR-T cell therapy, T lymphocytes with a synthetic CAR are utilized for identifying and subsequently erasing specific tumor cells, regardless of major histocompatibility complex (MHC) molecules [ 10 ]. … histocompatibility complex CD | cluster of differentiation TCR | T cell receptor ITAM | immuno-tyrosine activation motif ICOS | inducible T cell co-stimulator IL | interleukin FDA | Food and Drug Administration EMA | European Medicines Agency R/R | relapsed or refractory ORR | overall response rate …

Ferret coronavirus-associated diseases.

A novel coronavirus of ferrets was first described in 1993. This coronavirus caused an enteric disease called epizootic catarrhal enteritis (ECE). Recently, a ferret systemic coronavirus (FRSCV)-associated disease was discovered. This new systemic disease resembles the dry form of feline infectious peritonitis (FIP) and has been reported in the United States and Europe. This article addresses the clinical signs, pathology, pathogenesis, diagnosis, treatment, and prevention of this ferret FIP-like disease.

Systemic Sclerosis: From Pathophysiology to Novel Therapeutic Approaches.

Systemic sclerosis (SSc) is a systemic, immune-mediated chronic disorder characterized by small vessel alterations and progressive fibrosis of the skin and internal organs. The combination of a predisposing genetic background and triggering factors that causes a persistent activation of immune system at microvascular and tissue level is thought to be the pathogenetic driver of SSc. Endothelial alterations with subsequent myofibroblast activation, excessive extracellular matrix (ECM) deposition, and unrestrained tissue fibrosis are the pathogenetic steps responsible for the clinical manifestati

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… Comprehensive analysis of the major histocompatibility complex in systemic sclerosis identifies differential HLA associations by clinical and serological subtypes. Ann. Rheum. Dis. 2021;80:1040–1047. doi: 10.1136/annrheumdis-2021-219884. 16. Moroncini G., Baroni S.S., Gabrielli A. …

Use of Interferon Alfa in the Treatment of Myeloproliferative Neoplasms: Perspectives and Review of the Literature.

Interferon alfa was first used in the treatment of myeloproliferative neoplasms (MPNs) over 30 years ago. However, its initial use was hampered by its side effect profile and lack of official regulatory approval for MPN treatment. Recently, there has been renewed interest in the use of interferon in MPNs, given its potential disease-modifying effects, with associated molecular and histopathological responses. The development of pegylated formulations and, more recently, ropeginterferon alfa-2b has resulted in improved tolerability and further expansion of interferon's use. We review the evolvi

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… Studies have demonstrated that interferon augments T-cell, macrophage, and natural killer cell activity, and increases expression of tumor-associated and major histocompatibility complex antigens [ 28 , 29 , 30 ]. …

Gene Therapy for Pancreatic Diseases: Current Status.

The pancreas is a key organ involved in digestion and endocrine functions in the body. The major diseases of the pancreas include pancreatitis, pancreatic cancer, cystic diseases, pancreatic divisum, islet cell tumors, endocrine tumors, diabetes mellitus, and pancreatic pain induced by these diseases. While various therapeutic methodologies have been established to date, however, the improvement of conventional treatments and establishment of novel therapies are essential to improve the efficacy. For example, conventional therapeutic options, including chemotherapy, are not effective against p

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… In this study, high-resolution typing for HLA with sequence-based typing is utilized to determine whether certain alleles or haplotypes of major histocompatibility complex gene are associated with autoimmune pancreatitis. …

Innovative therapeutic concepts of progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is an opportunistic viral disease of the brain-caused by human polyomavirus 2. It affects patients whose immune system is compromised by a corresponding underlying disease or by drugs. Patients with an underlying lymphoproliferative disease have the worst prognosis with a mortality rate of up to 90%. Several therapeutic strategies have been proposed but failed to show any benefit so far. Therefore, the primary therapeutic strategy aims to reconstitute the impaired immune system to generate an effective endogenous antiviral response. Recently, an

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… Whereas initially peripheral mononuclear cells from seropositive donors were expanded ex vivo in a time-consuming manner, in the course of time it became possible to isolate virus-specific T cells with major histocompatibility complex (MHC)-multimers in a much more time-effective way [ 77 ]. …

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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… However, 10–20% of NK cells remain unlicensed, as they lack receptors for self-major histocompatibility complex (MHC) and are functionally hyporesponsive. … NKp44, a novel triggering surface molecule specifically expressed by activated natural killer cells, is involved in non-major histocompatibility complex-restricted tumor cell lysis. J Exp Med (1998) 187:2065–72. 10.1084/jem.187.12.2065 19. …

A new hope with CAR T-cell therapy for refractory idiopathic inflammatory myopathies: a systematic review.

BACKGROUND: Treatment options for refractory idiopathic inflammatory myopathies (IIMs) remain limited, and sustained remission is frequently not achieved with conventional immunosuppression or biologic agents. Chimeric antigen receptor (CAR) T-cell therapy has been approved for multiple refractory hematologic malignancies and is increasingly being explored as an immune reset strategy for autoimmune diseases. MAIN BODY: This Review synthesizes all available clinical evidence on CAR T-cell therapy in adult and pediatric IIM, with the aim of raising awareness within the rheumatology community re

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… CAR T cells are genetically engineered to recognize and eliminate target cells in a major histocompatibility complex (MHC)-independent manner, enabling highly specific and potent cytotoxic activity [ 9 ]. …

The anti-inflammatory effects of mesenchymal stem cells and their research progress in hematopoietic stem cell transplantation: A comprehensive review.

Hematopoietic stem cell transplantation (HSCT) is frequently accompanied by severe inflammation-related complications, among which graft-versus-host disease (GVHD) stands out as one of the most common and life-threatening. As a systemic inflammatory disorder, GVHD arises when donor T cells recognize the recipient's alloantigens and initiate an immune attack. Currently, effective second-line treatment options remain scarce for patients with antibiotic-resistant or steroid-refractory GVHD. Mesenchymal stem cells (MSCs) are non-hematopoietic cells widely distributed in fetal and adult tissues and

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… They are relatively easy to obtain and have low immunogenicity (e.g. low expression of major histocompatibility complex class II molecules and co-stimulatory molecules on their surface, making them less likely to trigger host immune rejection), laying a solid foundation for their clinical application …

Treatment of medulloblastoma using an oncolytic measles virus encoding the thyroidal sodium iodide symporter shows enhanced efficacy with radioiodine.

BackgroundMedulloblastoma is the most common malignant brain tumor of childhood. Although the clinical outcome for medulloblastoma patients has improved significantly, children afflicted with the disease frequently suffer from debilitating side effects related to the aggressive nature of currently available therapy. Alternative means for treating medulloblastoma are desperately needed. We have previously shown that oncolytic measles virus (MV) can selectively target and destroy medulloblastoma tumor cells in localized and disseminated models of the disease. MV-NIS, an oncolytic measles virus t

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… In mice, resistance and susceptibility to MV-induced encephalitis is governed by their major histocompatibility complex haplotype [ 37 ]. …

Human inhibitory leukocyte Ig-like receptors: from immunotolerance to immunotherapy.

In recent decades, immunotherapeutic strategies have been used to treat a wide range of pathologies, many of which were previously incurable, such as cancer and autoimmune disorders. Despite this unprecedented success, a considerable number of patients fail to respond to currently approved immunotherapies or develop resistance over time. Therefore, there is an urgent need to develop the next generation of immune-targeted therapies. Various members of the Ig superfamily play essential roles in regulating leukocyte functions. One such group, the leukocyte Ig-like receptors (LILRs), have been imp

Epigenome-Driven Strategies for Personalized Cancer Immunotherapy.

Fighting cancer remains one of the greatest challenges for science in the 21st century. Advances in immunotherapy against different types of cancer have greatly contributed to the treatment, remission, and cure of patients. In this context, knowledge of epigenetic phenomena, their relationship with tumor cells and how the immune system can be epigenetically modulated represent some of the greatest advances in the development of anticancer therapies. Epigenetics is a rapidly growing field that studies how environmental factors can affect gene expression without altering DNA sequence. Epigenomic

Treatment of Relapsed Acute Lymphocytic Leukemia in Adult Patients.

Opinion statementFor adult patients diagnosed with relapsed B cell-ALL (B-ALL), there have been significant improvements in available treatment options following the FDA approval of novel cellular and immunotherapy approaches - blinatumomab, chimeric antigen receptor (CAR) T therapy, and inotuzumab. For the last several years, research has focused on gaining a better understanding of the effects of specific disease and patient characteristics on long-term outcomes with each of the FDA-approved agents. In combination with the better prevention and management of unique, treatment-specific toxici

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… Both blinatumomab and the CD19 CAR therapies function by engaging the cytotoxic potential of T-cells without the need for T-cell receptor specificity, antigen processing/presentation, or major histocompatibility complex context [ 11 , 12 ]. …

Dawn of CAR-T cell therapy in autoimmune diseases.

AbstractChimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in the treatment of hematological malignancies. Based on the immunomodulatory capability of CAR-T cells, efforts have turned toward exploring their potential in treating autoimmune diseases. Bibliometric analysis of 210 records from 128 academic journals published by 372 institutions in 40 countries/regions indicates a growing number of publications on CAR-T therapy for autoimmune diseases, covering a range of subtypes such as systemic lupus erythematosus, multiple sclerosis, among others. CAR-T therapy hold

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… Introduction By reprogramming T cells to express chimeric antigen receptors (CARs) on their surface, CAR-T cells can harness the power of the self-immune system to fight malignant tumors in a non-major histocompatibility complex (MHC)-restricted manner, which has heralded a paradigm in cancer immunotherapy …

The Role of Monoclonal Antibodies in the Era of Bi-Specifics Antibodies and CAR T Cell Therapy in Multiple Myeloma.

Multiple myeloma (MM) remains largely incurable despite enormous improvement in the outcome of patients. Over the past decade, we have witnessed the "era of monoclonal antibody (moAb)", setting new benchmarks in clinical outcomes for relapsed and newly diagnosed MM. Due to their excellent efficacy and relative safe toxicity profile, moAbs in combination with immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) have become the new backbone of upfront anti-MM therapy. Yet, most patients will eventually relapse and patients who become refractory to IMiDs, PIs and moAbs have a dismal out

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… Bispecific Antibodies Bispecific antibody constructs bind MM cells through distinct targeted antigens and T cells through CD3 resulting in the killing of MM cells independent of major histocompatibility complex. …

Abstracts of the Cell Therapy Transplant Canada 2024 Annual Conference.

On behalf of Cell Therapy Transplant Canada (CTTC), we are pleased to present the Abstracts of the CTTC 2024 Annual Conference. The conference was held on 1-3 May 2024 in beautiful Victoria, British Columbia, at the Victoria Conference Centre, and attracted 293 in-person delegates and five virtual attendees. Several plenary sessions were held on topics such as gene therapy for hemoglobin disorders, optimizing donor selection, graft-versus-host disease (GvHD) strategies, collaborative care, survivorship, graft failure, and CAR-T therapy. Poster authors presented their work during a lively and e

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… Loss of heterozygosity (LOH) in major histocompatibility complex (MHC) genes or down-expression of MHC genes have been identified as a potential mechanism leading to relapse post-HCT. …

Efficacy of bortezomib as first-line treatment for patients with multiple myeloma.

Recent years have seen a dramatic change in the approach towards diagnosing and treating Multiple Myeloma. Newer and more target specific approach to treatment has prolonged the survival for patients with multiple myeloma. The proteasome inhibitors make an important class of anti-myeloma drugs that disrupts the proteolytic machinery of the tumor cells preferentially, enhancing their susceptibility to apoptosis. Bortezomib, in particular has shown significant clinical efficacy in myeloma treatment. It is the most commonly used proteasome inhibitor and has been tested to be effective in prolongi

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… Lactacystin and clasto-lactacystin beta-lactone modify multiple proteasome beta-subunits and inhibit intracellular protein degradation and major histocompatibility complex class I antigen presentation. J Biol Chem. 1997;272(20):13437–45. doi: 10.1074/jbc.272.20.13437. 33. Adams J SR. …