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Allogeneic Hematopoietic Transplantation for Multiple Myeloma in the New Drugs Era: A Platform to Cure.

Allogeneic hematopoietic cell transplantation (alloHCT) represents a treatment option for multiple myeloma (MM) patients. As shown in several studies, alloHCT is highly effective, but it is hampered by a high toxicity, mainly related to the graft-versus-host disease (GVHD), a complex immunological reaction ascribable to the donor's immune system. The morbidity and mortality associated with GVHD can weaken the benefits of this procedure. On the other side, the high therapeutic potential of alloHCT is also related to the donor's immune system, through immunological activity known as the graft-ve

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… DLI = Donor Lymphocyte Infusion; GVHD = Graft-Versus-Host Disease; IkB = Inhibitor of kB; NF-kB = Nuclear Factor-kB; MM = Multiple Myeloma; IkZF = Ikarus Zinc Finger; CAR = Chimeric Antigen Receptor; MHC Major Histocompatibility Complex; BCMA = B Cell Maturation Antige. …

Advances in cancer immunotherapy and future directions in personalized medicine.

Cancer immunotherapy has revolutionized oncologic treatment by harnessing and reprogramming the immune system to target malignant cells. This review provides a comprehensive picture of modern approaches to immunotherapy-based treatment strategies, such as immune checkpoint inhibitors (ICIs), chimeric antigen receptor T cells, mRNA vaccines, and biomaterials-based platforms, with a focus on their translational value and application to precision medicine. Emerging insights into the tumor microenvironment, immune resistance mechanisms, and T-cell subpopulation dynamics (e.g., γδ T cells, exhauste

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… These antigen presenting cells (APCs), namely, the dendritic cells (DCs), which then digest them and present them by the Major Histocompatibility Complex (MHC) on the surface of the naive T cells, despite the fact that a T-cell receptor (TCR) with an antigen-MHC, special signals are needed for the activation …

PD-1 as a potential target in cancer therapy.

Recently, an improved understanding of the molecular mechanisms governing the host response to tumors has led to the identification of checkpoint signaling pathways involved in limiting the anticancer immune response. One of the most critical checkpoint pathways responsible for mediating tumor-induced immune suppression is the programmed death-1 (PD-1) pathway, normally involved in promoting tolerance and preventing tissue damage in settings of chronic inflammation. Many human solid tumors express PD ligand 1 (PD-L1), and this is often associated with a worse prognosis. Tumor-infiltrating lymp

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… APC, antigen-presenting cell; IFN-γ, interferon gamma; MHC, major histocompatibility complex; PD-1, programmed death-1; PD-L1, PD ligand 1; TCR, T-cell receptor. …

Redefining the battle against colorectal cancer: a comprehensive review of emerging immunotherapies and their clinical efficacy.

Colorectal cancer (CRC) is the third most common cancer globally and presents a significant challenge owing to its high mortality rate and the limitations of traditional treatment options such as surgery, radiotherapy, and chemotherapy. While these treatments are foundational, they are often poorly effective owing to tumor resistance. Immunotherapy is a groundbreaking alternative that has recently emerged and offers new hope for success by exploiting the body's own immune system. This article aims to provide an extensive review of clinical trials evaluating the efficacy of various immunotherap

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… When mRNA vaccines are taken up by antigen-presenting cells (APCs), the epitopes of translated peptides are presented by their major histocompatibility complexes (MHCs), leading to the initiation of both CTL- and memory T-cell-dependent immune responses. … CAR, chimeric antigen receptor; TCR, T cell receptor; scFv, single-chain variable fragment; MHC, major histocompatibility complex. This figure is created with BioRender.com . Table 2 CAR-cells in clinical trials in CRC. Not Applicable (NA). …

Клинические интуиции и радиологические свойства на множестве склероза соединены с мигренью.

Фон: Множественный склероз (МС) и мигрень являются неврологическими заболеваниями, затрагивающими молодых женщин. Мигрейн является наиболее распространенным видом головной боли у людей с MS (PwMS). Цели: Цель настоящего обзора состоит в том, чтобы описать клинические, радиологические и терапевтические особенности МУ и коморбиды мигрени. В клинической части основное внимание уделяется характеристикам мигрени в ПУМС и MS в сопутствии с мигренью, а также на наличии других возможных коморбидов. Радиационная секция занимается дифференциальной диагностикой повреждений белой материи и изменениями в с

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… Although they did not find any evidence supporting migraine as a causal risk factor for MS, they identified four major histocompatibility complex (MHC) loci (genes HCG20, HLA-B, MSH5, TNXA, and TNXB) increasing the risk for both MS and migraine [ 10 ]. …

Blood biomarker dynamics in people with relapsing multiple sclerosis treated with cladribine tablets: results of the 2-year MAGNIFY-MS study.

BACKGROUND AND OBJECTIVES: Cladribine tablets (CladT) represent an effective immune reconstitution therapy, administered in short treatment courses over two consecutive years. To better understand the amplitude of immune changes, we performed a comprehensive analysis during the 2-year study period for the entire MAGNIFY-MS population (N=270). In addition to lymphocyte kinetics, we studied intracellular cytokines serum proteins, and their associations with clinical outcomes. To put these changes into perspective, we analyzed transcriptional changes in T and B cells and associated biological pat

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… BL, baseline; FDR, false discovery rate; IFN, interferon; Ig, immunoglobulin; IL, interleukin; MHC, major histocompatibility complex; M, month; NF, nuclear factor; PBMC, peripheral blood mononuclear cells. Gene expression of CD3 + and CD19 + cells at M12, M15 and M24 compared to BL. …

A Preliminary Investigation towards the Risk Stratification of Allogeneic Stem Cell Recipients with Respect to the Potential for Development of GVHD via Their Pre-Transplant Plasma Lipid and Metabolic Signature.

The clinical outcome of allogeneic hematopoietic stem cell transplantation (SCT) may be influenced by the metabolic status of the recipient following conditioning, which in turn may enable risk stratification with respect to the development of transplant-associated complications such as graft vs. host disease (GVHD). To better understand the impact of the metabolic profile of transplant recipients on post-transplant alloreactivity, we investigated the metabolic signature of 14 patients undergoing myeloablative conditioning followed by either human leukocyte antigen (HLA)-matched related or unr

Ready for Repair? Gene Editing Enters the Clinic for the Treatment of Human Disease.

We present an overview of clinical trials involving gene editing using clustered interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9), transcription activator-like effector nucleases (TALENs), or zinc finger nucleases (ZFNs) and discuss the underlying mechanisms. In cancer immunotherapy, gene editing is applied ex vivo in T cells, transgenic T cell receptor (tTCR)-T cells, or chimeric antigen receptor (CAR)-T cells to improve adoptive cell therapy for multiple cancer types. This involves knockouts of immune checkpoint regulators such as PD-1, components of the endo

Vaccines against human carcinomas: strategies to improve antitumor immune responses.

Multiple observations in preclinical and clinical studies support a role for the immune system in controlling tumor growth and progression. Various components of the innate and adaptive immune response are able to mediate tumor cell destruction; however, certain immune cell populations can also induce a protumor environment that favors tumor growth and the development of metastasis. Moreover, tumor cells themselves are equipped with various mechanisms that allow them to evade surveillance by the immune system. The goal of cancer vaccines is to induce a tumor-specific immune response that ultim

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… In order to avoid immune recognition, tumor cells have been shown to downregulate antigen expression, components of the antigen-processing and presentation machinery, and expression of major histocompatibility complex (MHC) molecules [ 17 ]. …

Antileukemia Activity of Human Natural Killer Cell-Derived Nanomagic Bullets against Acute Myeloid Leukemia (AML).

Background: Cancer is among the serious health problems of the medical world, for treatment of which severe treatments are used. However, the prognosis of cancer patients is still poor. The application of NK cell-derived exosomes (NK-Exo) is a new method for cancer immunotherapy. These nanoparticles with a size range of 30-120 nm are a small model of mother cells. In this study, the anti-tumor activity of NK-Exo and LAK-Exo (activated NK cell-derived exosome) against acute myeloid leukemia (AML) is investigated in vitro. Materials and Methods: The MACS method was performed for the separation o

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… NK cells are BM-derived large granular lymphocytes and a subset of innate lymphoid cells (ILCs).These cells can combat infectious and tumor cells through a variety pathways such as assessing the amount of major histocompatibility complex (MHC) class I proteins on the surface of tumor cells 13 - 15 . …

Review on Bortezomib Resistance in Multiple Myeloma and Potential Role of Emerging Technologies.

Multiple myeloma is a hematological cancer type. For its treatment, Bortezomib has been widely used. However, drug resistance to this effective chemotherapeutic has been developed for various reasons. 2D cell cultures and animal models have failed to understand the MM disease and Bortezomib resistance. It is therefore essential to utilize new technologies to reveal a complete molecular profile of the disease. In this review, we in-depth examined the possible molecular mechanisms that cause Bortezomib resistance and specifically addressed MM and Bortezomib resistance. Moreover, we also included

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… Down-regulation of the transporter for antigen presentation, proteasome subunits, and class I major histocompatibility complex in tumor cell lines. Cancer Res. 1998;58:3660–3667. 97. …

Natural Modulators of Endosomal Toll-Like Receptor-Mediated Psoriatic Skin Inflammation.

Psoriasis is a chronic inflammatory autoimmune disease that can be initiated by excessive activation of endosomal toll-like receptors (TLRs), particularly TLR7, TLR8, and TLR9. Therefore, inhibitors of endosomal TLR activation are being investigated for their ability to treat this disease. The currently approved biological drugs adalimumab, etanercept, infliximab, ustekinumab, ixekizumab, and secukizumab are antibodies against effector cytokines that participate in the initiation and development of psoriasis. Several immune modulatory oligonucleotides and small molecular weight compounds, incl

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… Searching for the major histocompatibility complex psoriasis susceptibility gene. The Journal of Investigative Dermatology. 2002;118(5):745–751. doi: 10.1046/j.1523-1747.2002.01749.x. 15. Nair R. P., Stuart P. E., Nistor I., et al. …

Significance of Medicinal Mushrooms in Integrative Oncology: A Narrative Review.

Medicinal mushrooms are widely used in East Asia for the treatment of various diseases, especially in complementary cancer care. While there is a growing interest in medicinal mushrooms in Western countries and an increasing number of pre-clinical studies indicate distinct anti-cancer and regenerative properties, little is known about their potential relevance for clinical practice. This review aims to provide an overview of the clinical evidence, significance and potential role of medicinal mushrooms in complementary cancer care. Scientific databases for (randomized) controlled clinical trial

Exosomes: A new option for osteoporosis treatment.

Osteoporosis is a systemic bone disease characterized by reduced bone mass and destruction of bone microarchitecture, leading to increased bone fragility and susceptibility to fracture. However, the pathogenesis and molecular mechanisms of this disease remain unclear. Extracellular vesicles, structures originating from the plasma membrane and ranging from 30 nm to 5 µm in diameter, play an important role in intercellular communication in the bone microenvironment. Exosomes are extracellular vesicles that deliver cargo molecules, including endogenous proteins, lipids and nucleic acids. These ca

Genetic Background of Medication-Related Osteonecrosis of the Jaw: Current Evidence and Future Perspectives.

Medication-related osteonecrosis of the jaw (MRONJ) is a rare side effect of antiresorptive drugs that significantly hinders the quality of life of affected patients. The disease develops in the presence of a combination of factors. Important pathogenetic factors include inflammation, inhibition of bone remodeling, or genetic predisposition. Since the first description of this rare side effect in 2003, a growing body of data has suggested a possible role for genetic factors in the disease. Several genes have been suggested to play an important role in the pathogenesis of MRONJ such as SIRT1, V

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… Major histocompatibility complex class II polymorphisms are associated with the development of anti-resorptive agent-induced osteonecrosis of the jaw J. Cranio-Maxillofac. Surg. 2013 41 71 75 10.1016/j.jcms.2012.10.018 23218978 105. Lee K.H. Kim S.H. Kim C.H. Min B.J. Kim G.J. Lim Y. Kim H.S. …

A Review of CAR-T Therapy in Pediatric and Young Adult B-Lineage Acute Leukemia: Clinical Perspectives in Singapore.

Approximately 10-15% of pediatric B-cell acute lymphoblastic leukemia (B-ALL) are high risk at diagnosis or relapsed/ refractory. Prior to the availability of chimeric antigen receptor T-cell (CAR-T) in Singapore and the region, the treatment options for these paediatric and young adults are conventional salvage chemotherapy or chemo-immunotherapy regimens as a bridge to allogeneic total body irradiation-based hematopoietic stem cell transplantation (allo-HSCT). This results in significant acute and long-term toxicities, with suboptimal survival outcomes. Finding a curative salvage therapy wit

The roles of curcumin in regulating the tumor immunosuppressive microenvironment.

Cancer is a harmful threat to human health. In addition to surgery, a variety of anticancer drugs are increasingly used in cancer therapy; however, despite the developments in multimodality treatment, the morbidity and mortality of patients with cancer patients are on the increase. The tumor-specific immunosuppressive microenvironment serves an important function in tumor tolerance and escape from immune surveillance leading to tumor progression. Therefore, identifying new drugs or foods that can enhance the tumor immune response is critical to develop improved cancer prevention methods and tr

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… Third, the lack of major histocompatibility complex class I on the surface of tumor cells can lead to the inability of the immune recognition of CD8+ cytotoxic T cells to mediate immune tolerance ( 63 ). …

The Role of the Ubiquitin System in Eye Diseases.

The ubiquitin-proteasome system (UPS) is a fundamental process that regulates various biological functions, including immune response, cell cycle, oxidative stress, migration, and cellular proliferation. This system is responsible for the degradation of proteins, while proteasomes play a significant role in mechanisms involved in health and human diseases. The participation of the UPS in immune response is particularly relevant, leading to the involvement of immunoproteasomes. This specialized proteasome is involved in the processing and presentation of antigenic peptides, making it crucial fo

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… Notably, it generates peptides for presentation by Major Histocompatibility Complex (MHC) class I molecules, a process essential for activating CD8+ T cells in response to viral infections [ 54 , 55 ]. …

Pathophysiological Roles of the CX3CL1-CX3CR1 Axis in Renal Disease, Cardiovascular Disease, and Cancer.

CX3CL1 and its unique receptor, CX3CR1, are leukocyte migration factors and are involved in the pathogenesis and progression of many inflammatory diseases and malignancies. The CX3CL1-CX3CR1 axis induces a variety of responses, including cell proliferation, migration, invasion, and apoptosis resistance. CX3CL1 is a transmembrane protein, and proteolysis generates a soluble form. The membrane and soluble forms of CX3CL1 exhibit different functions, but both bind to the chemokine receptor CX3CR1. The CX3CL1-CX3CR1 axis is a chemokine system that has attracted attention not only as a therapeutic

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… The IMs of major histocompatibility complex class II (MHC class II) high was significantly increased in CKD patients compared to healthy patients. When these MHC class II high IMs were stimulated with LPS, they produced more proinflammatory cytokines (TNF, IL-1β) than other subsets. …

Beyond BCMA: newer immune targets in myeloma.

AbstractThe identification and targeting of B-cell maturation antigen (BCMA) through immunotherapeutic strategies such as antibody-drug conjugates, chimeric antigen receptor T cells, and T-cell engagers have revolutionized the care of patients with multiple myeloma (MM). These treatment modalities have improved the survival outcomes of patients with relapsed and/or refractory MM compared with previously established strategies and are moving into earlier lines of therapy. Despite their efficacy, the majority of patients eventually relapse, necessitating additional therapeutic targets for salvag

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… The intracellular-derived targets are peptides presented on the tumor cell surface by major histocompatibility complex (MHC) class 1 molecules, and attempts have been made to create CAR T cells that recognize peptide-MHCs of interest. 65 , 66 One such example is NY-ESO-1 (New York esophageal squamous …