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Cytokine receptor IL27RA is an NF-κB-responsive gene involved in CD38 upregulation in multiple myeloma.

Multiple myeloma (MM) shows constitutive activation of canonical and noncanonical nuclear factor κB (NF-κB) signaling via genetic mutations or tumor microenvironment (TME) stimulations. A subset of MM cell lines showed dependency for cell growth and survival on the canonical NF-κB transcription factor RELA alone, suggesting a critical role for a RELA-mediated biological program in MM pathogenesis. Here, we determined the RELA-dependent transcriptional program in MM cell lines and found the expression of the cell surface molecules interleukin-27 receptor-α (IL-27Rα) and the adhesion molecule JA

Модулятор течения VRAC 1 Потенциальная цель в множественных склерозах.

Множественный склероз (MS) — хроническое иммунопосредованное демиелинирующее заболевание ЦНС. Подчёркиваемый успехом таких методов лечения, разрушающих клетки В, как моноклональные anti-CD20 Клетки антител ritoximab, ocrelizumab и atumumumab, B играют центральную роль в иммунопатологии болезни. Однако целевые антигены патогенной реакции B-клеток в MS остаются неясными. Мы комбинировали поликлональную стимуляцию B-клеток периферийных мононуклеарных клеток крови с микроаварией протеомного протеина по всему организму человека для выявления целевых антигенов MS путем сопоставления образцов из 20 б

CAR-T cell therapies in autoimmune rheumatic diseases: a brief report on the clinical trial landscape, current status, and future perspectives.

Autoimmune rheumatic diseases (ARDs) are chronic inflammatory disorders where B cells play a key role. Traditional B-cell-targeted therapies have limitations, whereas CAR-T-cell therapy, which aims for a broader reset of the B-cell compartment by targeting B-cell surface markers such as CD19 or B-cell maturation antigen (BCMA), has unique advantages. Currently, most CAR-T cell trials for ARDs are in the early stages, with 64.29% (36/56 trials) of studies being phase I trials and only 7.14% (4/56 trials) progressing to phase II trials, primarily focusing on conditions, such as systemic lupus er

Chemokines: humble yet mighty players in the tumour microenvironment.

Chemokines are tiny chemotactic cytokines which play a crucial role in pathophysiology by maintaining homeostasis and inflammation. Their role in the tumour microenvironment is very much puzzling because of both pro- and anti-tumourigenic effects. Chemokines have gained much attention today, since it has been recognized that they are game changers in the TME via controlling immune cell recruitment, angiogenesis, metastasis, tumour growth and drug resistance. In this review, we are exploring the role of several chemokines and their receptors in the TME with special focus on immune cell recruitm

Direct immunoactivation by chemotherapeutic drugs in cancer treatment.

The immune system plays a crucial role in recognizing and eliminating pathogenic substances and malignant cells in the body. For cancer treatment, immunotherapy is becoming the standard treatment for many types of cancer and is often combined with chemotherapy. Although chemotherapeutic agents are often reported to have adverse effects, including immunosuppression, they can also play a positive role in immunotherapy by directly stimulating the immune system. This has been demonstrated in preclinical and clinical studies in the past decades. Chemotherapeutics can activate immune cells through d

The progress and perspective of nanomedicine in modulating the tumor immune microenvironment.

The widespread application of nanomedicine in oncology is reshaping cancer treatment paradigms. Using the precise targeting mechanisms and the rapid advancements in nanoscale materials, nanomedicine is driving progress in cancer therapy, particularly within the complex landscape of the tumor immune microenvironment (TIM). This review provides a comprehensive overview of recent studies elucidating the critical role of nanomedicine in modulating the TIM, augmenting the efficacy of immunotherapies, and overcoming therapeutic resistance. Emphasis is placed on the significance of targeted drug deli

Высокоэффективная терапия для предотвращения образования лимфоидных органов менингеля после скрининга индекса CXCL13 при раннем множественном склерозе.

Посмертные исследования показали наличие подпийного воспаления с высшими лимфоидными органами (ТЛО) в менингах пациентов с прогрессивным множественным склерозом, играющих важную роль в патофизиологии болезни. Химокин (C-X-C-motif) лиганд 13 (CXCL13) вызывает образование этих лимфоидных органов, тем самым поощряя активность болезни. Заболеваемость при множественном склерозе сократилась благодаря воздействию изменяющейся терапии. Однако, несмотря на успехи в лечении болезней иммуномодуляционными агентами, у нас по-прежнему нет специальных лабораторных биомаркеров, которые могли бы указывать на с

Areas of Uncertainty in SARS-CoV-2 Vaccination for Cancer Patients.

Early in the COVID-19 pandemic, it was recognized that infection with SARS-CoV-2 is associated with increased morbidity and mortality in patients with cancer; therefore, preventive vaccination in cancer survivors is expected to be particularly impactful. Heterogeneity in how a neoplastic disease diagnosis and treatment interferes with humoral and cellular immunity, however, poses a number of challenges in vaccination strategies. Herein, the available literature on the effectiveness of COVID-19 vaccines among patients with cancer is critically appraised under the lens of anti-neoplastic treatme

Role of Bruton's tyrosine kinase in B cells and malignancies.

Bruton's tyrosine kinase (BTK) is a non-receptor kinase that plays a crucial role in oncogenic signaling that is critical for proliferation and survival of leukemic cells in many B cell malignancies. BTK was initially shown to be defective in the primary immunodeficiency X-linked agammaglobulinemia (XLA) and is essential both for B cell development and function of mature B cells. Shortly after its discovery, BTK was placed in the signal transduction pathway downstream of the B cell antigen receptor (BCR). More recently, small-molecule inhibitors of this kinase have shown excellent anti-tumor a

Clinical impact of checkpoint inhibitors as novel cancer therapies.

Immune responses are tightly regulated via signaling through numerous co-stimulatory and co-inhibitory molecules. Exploitation of these immune checkpoint pathways is one of the mechanisms by which tumors evade and/or escape the immune system. A growing understanding of the biology of immune checkpoints and tumor immunology has led to the development of monoclonal antibodies designed to target co-stimulatory and co-inhibitory molecules in order to re-engage the immune system and restore antitumor immune responses. Anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibodies were among t

Tumor buster - where will the CAR-T cell therapy 'missile' go?

Chimeric antigen receptor (CAR) T cell (CAR-T cell) therapy based on gene editing technology represents a significant breakthrough in personalized immunotherapy for human cancer. This strategy uses genetic modification to enable T cells to target tumor-specific antigens, attack specific cancer cells, and bypass tumor cell apoptosis avoidance mechanisms to some extent. This method has been extensively used to treat hematologic diseases, but the therapeutic effect in solid tumors is not ideal. Tumor antigen escape, treatment-related toxicity, and the immunosuppressive tumor microenvironment (TME

Targeted treatment of autoimmune cytopenias in primary immunodeficiencies.

Primary Immunodeficiencies (PID) are a group of rare congenital disorders of the immune system. Autoimmune cytopenia (AIC) represents the most common autoimmune manifestation in PID patients. Treatment of AIC in PID patients can be really challenging, since they are often chronic, relapsing and refractory to first line therapies, thus requiring a broad variety of alternative therapeutic options. Moreover, immunosuppression should be fine balanced considering the increased susceptibility to infections in these patients. Specific therapeutic guidelines for AIC in PID patients are lacking. Treatm

Spectrum of Movement Disorders in Hematological Malignancies: A Comprehensive Systematic Review of Clinical Phenotypes, Mechanisms, and Outcomes.

BACKGROUND: Movement disorders associated with hematologic malignancies remain incompletely defined. This review synthesized published articles to clarify clinical patterns, mechanisms, and outcomes across hematologic malignancies. METHODS: A PRISMA-compliant systematic search of PubMed, Embase, Scopus, and Google Scholar was conducted to identify reports describing movement disorders associated with hematologic malignancies. Eligible reports were screened according to predefined criteria, and data were extracted on demographics, hematologic diagnosis, central nervous system (CNS) involvement

A Systematic Pan-Cancer Analysis of YY1 Aberrations and their Relationship with Clinical Outcome, Tumor Microenvironment, and Therapeutic Targets.

Yin-Yang 1 (YY1) has a crucial function in the development of several malignancies, according to recent research. However, nothing is known about its aberrant expression and prognostic significance in human pan-cancer. We first explored the potential carcinogenic effect of YY1 in 33 cancers using the cancer genome atlas (TCGA) project and gene expression omnibus (GEO) datasets in this research. Then, we contained a variety of elements, for instance, gene expression, the state of survival, gene alterations, protein phosphorylation, immune infiltration, and related cellular pathways, and used a

The Insider: Impact of the Gut Microbiota on Cancer Immunity and Response to Therapies in Multiple Myeloma.

The human microbiota is a unique set of microorganisms colonizing the human body and evolving within it from the very beginning. Acting as an insider, the microbiota provides nutrients, and mutualistically interacts with the host's immune system, thus contributing to the generation of barriers against pathogens. While a strong link has been documented between intestinal dysbiosis (i.e., disruption to the microbiota homeostasis) and diseases, the mechanisms by which commensal bacteria impact a wide spectrum of mucosal and extramucosal human disorders have only partially been deciphered. This is

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… Gut Microbiota Drive Autoimmune Arthritis by Promoting Differentiation and Migration of Peyer’s Patch T Follicular Helper Cells. Immunity (2016) 44:875–88. doi: 10.1016/j.immuni.2016.03.013 28. Linehan JL, Harrison OJ, Han SJ, Byrd AL, Vujkovic-Cvijin I, Villarino AV, et al. …

Common gamma chain cytokines-driven optimization of chimeric antigen receptor T cells: Mechanistic insights and future directions.

Malignant tumors represent a major threat to human life and health, posing persistent challenges in medical research. While chimeric antigen receptor T (CAR-T) cell therapy has demonstrated breakthrough efficacy in hematological malignancies such as leukemia and lymphoma, its application in solid tumors, including hepatocellular carcinoma, lung cancer, and pancreatic cancer, remains constrained by multiple bottlenecks. These limitations encompass the immunosuppressive tumor microenvironment, insufficient in vivo persistence of CAR-T cells, long-term treatment-induced exhaustion, and off-target

Assessment of a Systematic Screening of Occupational Exposures in Malignant Hemopathies in the Rhone-Alpes Area: Prolymphome Study.

BACKGROUND: Several studies have highlighted the role of environmental exposures in malignant hemopathies etiology. Some patients with malignant hemopathies can be compensated as occupational diseases. The Prolymphome research aimed to assess a systematic screening of occupational exposures in patients with lymphoma or myeloma treated in three hospitals in the Rhône-Alpes region. METHODS: Patients received a self-administered questionnaire to fill in at home to collect their job history and potential occupational exposures to carcinogens. A physician assessed the questionnaire to determine if

Pathogenetic Mechanisms Linking Sarcoidosis to Lymphoma.

Sarcoidosis and lymphoma share immunopathological characteristics that suggest a complex, interconnected relationship. This article examines the multi-faceted mechanisms linking sarcoidosis to lymphoma, a phenomenon called sarcoidosis-lymphoma syndrome (SLS). SLS is hard to diagnose, requiring distinct criteria and imaging to differentiate overlapping features and histological differences. The co-occurrence of these diseases may be explained by genetic predispositions, immune dysregulation, and environmental factors that enhance malignancy risk. In active sarcoidosis, chronic inflammation and

Advances in the Pathogenesis and Treatment of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a genetically predisposed, female-predominant disease, characterized by multiple organ damage, that in its most severe forms can be life-threatening. The pathogenesis of SLE is complex and involves cells of both innate and adaptive immunity. The distinguishing feature of SLE is the production of autoantibodies, with the formation of immune complexes that precipitate at the vascular level, causing organ damage. Although progress in understanding the pathogenesis of SLE has been slower than in other rheumatic diseases, new knowledge has recently led to the d

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… Cell distance mapping identifies functional T follicular helper cells in inflamed human renal tissue Sci. Transl. Med. 2014 6 230ra246 10.1126/scitranslmed.3008146 24695686 PMC4129446 56. Comte D. Karampetsou M.P. Yoshida N. Kis-Toth K. Kyttaris V.C. Tsokos G.C. …

Immune checkpoint blockade in the treatment of malignant tumor: current statue and future strategies.

After being stagnant for decades, there has finally been a paradigm shift in the treatment of cancer with the emergence and application of immune checkpoint inhibitors (ICIs). The most extensively utilized ICIs are targeting the pathways involving programmed death-1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4). PD-1, as an crucial immune inhibitory molecule, by and large reasons the immune checkpoint response of T cells, making tumor cells get away from immune surveillance. Programmed cell death ligand-1 (PD-L1) is exceptionally expressed in most cancers cells and approves n