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Unlocking the Heterogeneity in Acute Leukaemia: Dissection of Clonal Architecture and Metabolic Properties for Clinical Interventions.

Genetic studies of haematological cancers have pointed out the heterogeneity of leukaemia in its different subpopulations, with distinct mutations and characteristics, impacting the treatment response. Next-generation sequencing (NGS) and genome-wide analyses, as well as single-cell technologies, have offered unprecedented insights into the clonal heterogeneity within the same tumour. A key component of this heterogeneity that remains unexplored is the intracellular metabolome, a dynamic network that determines cell functions, signalling, epigenome regulation, immunity and inflammation. Unders

Research progress on the anti-cancer mechanisms of edible salty-flavored Chinese materia medica.

Edible salty-flavored Chinese materia medica (ESCM) refers to a category of traditional Chinese medicine (TCM) that also serve as food, characterized by their salty flavor. According to the TCM theory, ESCM can soften and disperse knots, thus potentially offering benefits for cancer prevention and treatment. With cancer remaining a major global health challenge, its primary prevention strategies, especially through dietary modification, are crucial. ESCM have recently garnered substantial attention, due to their remarkable clinical efficacy and low side-effect profile. Researches on ESCM demon

Myeloid-Derived Suppressor Cells in Sepsis: Pathophysiology, Duality, and Therapeutic Frontiers.

Sepsis-induced immunosuppression, one of the factors contributing to mortality, is closely mediated by myeloid-derived suppressor cells (MDSCs). This review first outlines MDSC biology, describing their origin from pathological emergency myelopoiesis and classification into polymorphonuclear and monocytic subsets. We then discuss their dual role: an early, protective modulation of cytokine storm that later evolves into harmful immunosuppression associated with secondary infections and death. The underlying mechanisms involve L-arginine depletion ( via arginase 1/inducible nitric oxide synthase

Brain intratumoural astatine-211 radiotherapy targeting syndecan-1 leads to durable glioblastoma remission and immune memory in female mice.

BackgroundGlioblastoma (GB), the most aggressive brain cancer, remains a critical clinical challenge due to its resistance to conventional treatments. Here, we introduce a locoregional targeted-α-therapy (TAT) with the rat monoclonal antibody 9E7.4 targeting murine syndecan-1 (SDC1) coupled to the α-emitter radionuclide astatine-211 (211At-9E7.4).MethodsWe orthotopically transplanted 50,000 GL261 cells of murine GB into the right striatum of syngeneic female C57BL/6JRj mice using stereotaxis. After MRI validation of tumour presence at day 11, TAT was injected at the same coordinates. Biodistri

Chimeric antigen receptor-based cell therapy for treating urological tumors.

Urological tumors represent a significant global health challenge, with conventional therapies often proving insufficient to control disease progression. Recent breakthroughs in cellular immunotherapy, particularly in chimeric antigen receptor (CAR)-T cell, CAR-natural killer cell, and CAR-macrophage therapies, have demonstrated remarkable potential for treating these malignancies. Ongoing research is actively refining CAR-based strategies to enhance their precision in targeting tumor-associated antigens. This review comprehensively summarizes the applications of CAR cell therapy in the follow

UEG Week 2017 Oral Presentations

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Dynamic roles of inflammasomes in inflammatory tumor microenvironment.

The inflammatory tumor microenvironment has been known to be closely connected to all stages of cancer development, including initiation, promotion, and progression. Systemic inflammation in the tumor microenvironment is increasingly being recognized as an important prognostic marker in cancer patients. Inflammasomes are master regulators in the first line of host defense for the initiation of innate immune responses. Inflammasomes sense pathogen-associated molecular patterns and damage-associated molecular patterns, following recruitment of immune cells into infection sites. Therefore, dysreg

Gut microbiota shapes cancer immunotherapy responses.

The gut microbiota significantly influences cancer immunotherapy efficacy by modulating immune responses, remodeling the tumor microenvironment (TME), and producing key metabolites. Strategies such as FMT, probiotics, and dietary interventions show promise in enhancing responses to ICIs and ACTs while reducing immune-related adverse events (irAEs). This review summarizes clinical and preclinical findings and discusses microbiota-based interventions and future directions for precision immunotherapy.

CAR T cells and T cell engagers for autoimmunity-lessons from hematology.

Autoimmune diseases are driven by dysregulated immune responses against self-antigens, resulting in chronic inflammation and progressive tissue damage. Chimeric antigen receptor (CAR) T cell therapy and T cell engagers, initially developed for the treatment of hematologic malignancies, have demonstrated that they can mediate profound and sustained depletion of pathogenic B cells, leading to long-term remissions in otherwise refractory diseases. In this review, we explore key insights gained from hematologic applications of CAR T cells and T cell engagers, and discuss how these lessons can guid

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… Dynamic biomarkers, such as CAR T-cell expansion kinetics, inflammatory signatures, antigen evolution, and circulating tumor DNA, can inform dose adjustments, timing of repeat infusions, or supportive interventions to maintain long-term disease control. …

Correlation analysis of serum CCL3, TRACP-5b, and sclerostin with the prognosis of multiple myeloma patients.

BACKGROUND: To investigate the clinical use of Sclerostin, tartrate-resistant acid phosphatase 5b (TRACP-5b), and serum C-C motif chemokine ligand 3 (CCL3) levels in assessing the health and prognosis of patients with multiple myeloma. METHODS: A total of 250 patients with multiple myeloma who visited the hospital between January 2023 and December 2024 were included as the observation group, while 150 healthy individuals evaluated during the same period served as the control group. Serum levels of CCL3, TRACP-5b, and Sclerostin were measured and compared in the observation group before and aft

A Comprehensive Biological and Clinical Perspective Can Drive a Patient-Tailored Approach to Multiple Myeloma: Bridging the Gaps between the Plasma Cell and the Neoplastic Niche.

There is a broad spectrum of diseases labeled as multiple myeloma (MM). This is due not only to the composite prognostic risk factors leading to different clinical outcomes and responses to treatments but also to the composite tumor microenvironment that is involved in a vicious cycle with the MM plasma cells. New therapeutic strategies have improved MM patients' chances of survival. Nevertheless, certain patients' subgroups have a particularly unfavorable prognosis. Biological stratification can be subdivided into patient, disease, or therapy-related factors. Alternatively, the biological sig

TGF-β in hematologic malignancies: molecular functions and clinical applications.

Transforming growth factor-β (TGF-β) represents a family of multifunctional cytokines, primarily secreted by megakaryocytes, monocytes, T lymphocytes, bone marrow stromal cells, and other cell types. TGF-β plays an essential role in various physiological processes, including the regulation of cell proliferation, differentiation, apoptosis, and immune homeostasis. As a key immunoregulatory cytokine, TGF-β contributes to an immunosuppressive network within the microenvironment of hematologic malignancies by modulating the functions of both adaptive and innate immune cells. Current studies have s

Abstracts from the ISSAID 2021 Periodic Congress : Virtual. May - Dec 2021

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Immunosuppressants/Immunomodulators and Malignancy.

Individuals with immunosuppressive conditions are at a higher risk of developing malignancies than those in the general population. Immunosuppression weakens tumor immunity, hinders the detection of pro-oncogenic cells, and activates oncogenic viruses. Malignancies arising in immunosuppressed patients tend to be aggressive, have a high incidence of virus-associated cancers, and are reversible in some cases. Notably, immunosuppressive agents influence the frequency and type of malignancies, as well as their clinicopathological features. Organ transplant recipients receive long-term immunosuppre

Potential Targeting Mechanisms for Bone-Directed Therapies.

Bone development is characterized by complex regulation mechanisms, including signal transduction and transcription factor-related pathways, glycobiological processes, cellular interactions, transportation mechanisms, and, importantly, chemical formation resulting from hydroxyapatite. Any abnormal regulation in the bone development processes causes skeletal system-related problems. To some extent, the avascularity of cartilage and bone makes drug delivery more challenging than that of soft tissues. Recent studies have implemented many novel bone-targeting approaches to overcome drawbacks. Howe

Restoring the Immunity in the Tumor Microenvironment: Insights into Immunogenic Cell Death in Onco-Therapies.

Immunogenic cell death (ICD) elicited by cancer therapy reshapes the tumor immune microenvironment. A long-term adaptative immune response can be initiated by modulating cell death by therapeutic approaches. Here, the major hallmarks of ICD, endoplasmic reticulum (ER) stress, and damage-associated molecular patterns (DAMPs) are correlated with ICD inducers used in clinical practice to enhance antitumoral activity by suppressing tumor immune evasion. Approaches to monitoring the ICD triggered by antitumoral therapeutics in the tumor microenvironment (TME) and novel perspective in this immune sy

Bispecific Monoclonal Antibodies in Diffuse Large B-Cell Lymphoma: Dawn of a New Era in Targeted Therapy.

Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma (NHL) worldwide. Currently, approximately sixty percent of patients are cured with R-CHOP as frontline treatment, while the remaining patients experience primary refractory or relapsed (R/R) disease. Recently, the introduction of Pola-R-CHP as front-line therapy has represented a major advance in the management of DLBCL, resulting in improved outcomes. Prognosis of R/R DLBCL patients is poor, particularly for those eligible neither for chimeric antigen receptor (CAR) T-cell therapy nor autologous stem cell

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… The NCT04980222 trial is evaluating the safety and efficacy of glofitamab + R-CHOP in LBCL defined as high-risk by circulating tumor DNA (ctDNA) dynamics. Preliminary results showed an ORR of 93.3% and a CR rate of 80% at EOT [ 55 ]. … Glofitamab (Glofit) Plus R-CHOP Has a Favorable Safety Profile and Induces High Response Rates in Patients with Previously Untreated (1L) Large B-Cell Lymphoma (LBCL) Defined As High Risk By Circulating Tumor DNA (CtDNA) Dynamics: Preliminary Safety and Efficacy Results. …

Ten tips for an onco-nephrology clinic.

An increasing number of cancer patients are benefiting from long term cancer-directed therapy with an ever-expanding arsenal of novel agents from monoclonal antibodies to small molecules and cellular therapies in addition to the mainstay cytotoxic chemotherapy. All these therapies are accompanied by a unique array of adverse events, which include kidney toxicity. In this context, the need for onco-nephrology expertise continues to grow. Oncologists and hematologists collaborate closely with onco-nephrologists to determine: (i) treatment options for special populations based on accurate assessm

Multiple Myeloma Cell-Derived Exosomes: Implications on Tumorigenesis, Diagnosis, Prognosis and Therapeutic Strategies.

Multiple myeloma (MM) is a hematological disease that is still not curable. The bone marrow milieu, with cellular and non-cellular elements, participate in the creation of a pro-tumoral environment enhancing growth and survival of MM plasma cells. Exosomes are vesicles oscillating in dimension between 50 nm and 100 nm in size that can be released by various cells and contribute to the pathogenesis and progression of MM. Exosomes enclose proteins, cytokines, lipids, microRNAs, long noncoding RNAs, and circular RNAs able to regulate interactions between MM plasma cells and adjacent cells. Throug

A Rare and Fatal Case of Hemophagocytic Lymphohistiocytosis Associated with Sarcoidosis.

BACKGROUND Sarcoidosis is a systemic inflammatory disorder characterized by a classic pathologic feature of non-caseating granulomas involving any organ system. Hemophagocytic lymphohistiocytosis (HLH) is a catastrophic cytokine surge characterized by dysregulation of the macrophage response, which can be rapidly fatal. Recognition of HLH has been increasing over the past decade. HLH can present with features of sepsis that can make the diagnosis challenging and requires high clinical suspicion. CASE REPORT We report a case of a 48-year-old African American male with a past medical history of