Endometrial cancer (EC) is one of the most frequent gynecologic cancers worldwide. Therapeutic interventions, including surgery, are known to alter immune cell populations and the tumor microenvironment. Among these, Myeloid-derived suppressor cells (MDSC), a heterogeneous population of immature myeloid cells with potent immunosuppressive activity, play an important role in cancer progression. The present study analyzed the frequencies of monocytic MDSC (M-MDSC), early-stage MDSC (e-MDSC), and polymorphonuclear (PMN-MDSC) subsets in PBMC using flow cytometry and quantified Arginase-1 serum levels by ELISA. Our results showed that M-MDSC and PMN-MDSC frequencies were increased in patients compared with healthy donors and decreased following surgery, whereas no changes were observed in e-MDSC percentages. Across MDSC subtypes, the percentages of SIRP-α-, CD73-, PD-L1-, and Galectin-9-positive cells were higher in pre- and post-surgery EC samples than in healthy donors. Notably, in the case of Galectin-9, M-MDSC and PMN-MDSC positive to this receptor were increased before surgery and decreased after surgery, parallel to the changes in M-MDSC and PMN-MDSC frequencies, suggesting a possible role for Galectin-9 in MDSC proliferation. Arginase-1 serum levels also decreased after surgery. In conclusion, our results demonstrate that endometrial cancer patients exhibit differential percentages of MDSC and receptor expression, which are influenced by surgical intervention. It is important to highlight Galectin-9 expression, as it may have a postoperative prognostic role. Future studies are warranted to clarify the prognostic utility of these molecules in endometrial cancer patients.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder associated with dementia, progressive neuronal loss, extracellular amyloid-β (Aβ) and intracellular hyperphosphorylated tau deposition. Currently, no curative therapies are available for this condition. Beyond these features, AD pathogenesis is associated with neuroinflammation, which is thought to be primarily driven by microglial cells, and has evolved as an important contributor to AD pathogenesis over the past decade. Although microglia cells play a central role in neuroinflammation, they are also a highly heterogeneous population existing in distinct transcriptional states that can be either beneficial or detrimental to disease progression. Importantly, microglial activation and the ensuing neuroinflammatory milieu do not operate independently of the systemic immune system. The longstanding view of the brain as an immune-privileged organ has been fundamentally revised, with increasing evidence demonstrating that the crosstalk between brain-resident and circulating peripheral immune cells plays a pivotal role in AD pathogenesis. Peripheral immune cells, recruited in the central nervous system in response to Aβ and tau pathology, actively modulate the neuroinflammatory environment. While CD4[+] and CD8[+] T cells have been extensively investigated in this context, the contribution of B cells to AD remains poorly understood. Here, we comprehensively review the phenotypic and functional alterations of B cells in AD, integrating evidence from experimental models and human studies, to evaluate whether B cells constitute an underappreciated component of the adaptive immune response in AD and whether they represent a compelling immunotherapeutic target. We also highlight key unresolved questions and propose future research directions to guide the field towards a deeper mechanistic understanding of B cell biology in AD.

Hemoglobin-based oxygen carriers (HBOCs) are blood substitutes utilized for oxygen delivery, but their systemic effects on immune homeostasis remain insufficiently characterized. In this study, healthy C57BL/6J mice were intravenously administered with either HBOC (RedpCarrier, 600 mg/kg/day) or vehicle for three consecutive days. Using single-cell RNA sequencing (scRNA-seq), we generated a comprehensive transcriptomic atlas of bone marrow (BM) leukocytes. Unbiased clustering revealed that HBOC exposure significantly remodeled the BM landscape, characterized by a proportional decrease in neutrophils and monocytes alongside an expansion of B cells, T cells, and dendritic cells. Quantitative analysis identified 124 significantly upregulated genes across immune compartments, which were overwhelmingly enriched in Type-I interferon signaling and defense responses to viruses. The interferon-stimulated gene Isg15 was identified as a core upregulated marker across multiple lineages. To evaluate functional outcomes, we employed lethal SARS-CoV-2 and HSV-1 infection models, where HBOC-pretreated mice exhibited significantly higher 14-day survival rates compared to controls. In summary, our findings demonstrate that HBOC administration induces a distinctive antiviral-like transcriptional priming state within the bone marrow microenvironment. Crucially, in vitro functional assays and protein-level validations confirm that high-dose HBOC treatment drives intracellular ROS accumulation and subsequently activates Stat1 expression and phosphorylation in macrophages. Together, these transcriptomic and experimental insights establish a solid mechanistic link between HBOC-induced redox modulation and innate immune activation, providing a foundational framework for exploring HBOCs as potential adjunctive immunomodulators for enhanced viral defense.

Autoreactive T and B cells recognizing tissue-associated self-antigens are tolerized in the periphery, where dendritic cells (DCs) initiate the inactivation of autoreactive T cells. Here, we generated a mouse model in which a neo-self-antigen is expressed in the epidermis and examined interactions between DCs and antigen-specific CD4 T cells, as well as between CD4 T cells and B cells under tolerant conditions. We found that one of the tumor necrosis factor receptor superfamily (TNFRSF) molecules, herpesvirus entry mediator (HVEM), in CD4 T cells performs two key functions: it promotes regulatory T cell (Treg) expansion in response to epidermal antigen and suppresses B cell activation by sending inhibitory signals. HVEM-deficient Tregs failed to respond to self-antigen-loaded migratory DCs from the skin, whereas HVEM-deficient CD4 T cells enhanced B cell activation, leading to increased IgG1[+] B cells. These findings demonstrate that HVEM in CD4 T cells contributes to peripheral tolerance to tissue-associated self-antigens by promoting Treg expansion and restraining B cell responses.

The common marmoset (Callithrix jacchus) is a valuable non-human primate model organism with a long history of use in biomedical research, including investigating diseases with an immune component. However, prior to this effort, there has been a lack of sufficiently validated tools to quantify inflammatory markers in the common marmoset using a multiplex approach. We provide a cross-species reactivity validation of a human-specific multiplex analysis strategy that allows for the assessment of 20 distinct inflammatory analytes in a small volume of plasma isolated from common marmoset blood. We used this novel approach to perform an assessment of the impact of sex as a biological variable on a subset of these inflammatory analytes. We found that endogenous plasma levels of the following analytes are not significantly different between female and male marmosets: CRP, ICAM-1, VCAM-1, IL-13, IL-8, MIP-1β, IFN-g, IL-4, VEGF-A, FLT-1, and bFGF. These findings demonstrate the utility of our validated method for quantifying marmoset inflammatory markers.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive malignancies with limited diagnostic and prognostic markers. Neutrophil extracellular traps (NETs) have recently been implicated in cancer progression, but their clinical relevance in PDAC remains underexplored. In this preliminary study, we investigated NET levels in both peripheral blood and tumor tissues from PDAC patients (n = 30) and explored their associations with clinicopathological features. We quantified NETs using a multiparametric approach that included immunohistochemistry, immunofluorescence, qRT-PCR, ELISA, and flow cytometry. Plasma NET-associated DNA was measured using the Quant-iT PicoGreen assay. Receiver operating characteristic (ROC) analysis was performed to assess the diagnostic potential of NETs. We found NET levels were significantly elevated in both tumor tissue and the circulation of PDAC patients compared with healthy controls. The levels of NETs were strikingly higher in patients with advanced tumor stages and grades. Patients' NETs showed a typical morphology with enlarged nuclei, thread-like DNA fibres, and MPO-positive granules, which was confirmed by immunofluorescence analysis. The ROC analysis demonstrated that NETs displayed promising diagnostic performance (AUC = 0.852) compared to widely used conventional markers CEA and CA19-9 within the study cohort. In conclusion, our findings provide preliminary evidence that increased NETosis is associated with PDAC progression and highlight its potential as a diagnostic biomarker. Larger, independent studies are needed to validate these observations and to determine the clinical relevance of NET-associated markers in PDAC.

The neonatal Fc receptor (FcRn) recycles immunoglobulin G (IgG) in cells and is responsible for the long half-life of IgG relative to other plasma proteins. FcRn also recycles pathogenic IgG autoantibodies and is the target for several new targeted therapeutic agents in IgG autoantibody-driven disorders. These therapeutics include rozanolixizumab, a high-affinity monoclonal antibody that directly blocks the IgG binding site on FcRn in a pH-independent manner. This study explored the impact of these molecular characteristics on rozanolixizumab's cellular uptake, endosomal trafficking and recycling. Another anti-FcRn therapeutic, the Fc fragment MST-HN IgG Fc (an analog of efgartigimod), a competitive antagonist with weaker affinity and pH-dependent binding to FcRn, was included for comparison. Using high-content imaging methods in human umbilical vein endothelial cells (HUVECs), a time- and concentration-dependent uptake of fluorescently labeled rozanolixizumab into intracellular compartments was observed. Uptake was rapid, pH-independent, and competed out with unlabeled inhibitor, supporting a receptor-mediated mechanism. Conversely, uptake of MST-HN IgG Fc was slower and required higher concentrations to detect uptake, which was pH-dependent, not competed out with unlabeled inhibitor, and occurred with similar potency in cells that did not express FcRn, suggesting a receptor-independent mechanism such as fluid phase pinocytosis. Using Rab proteins associated with different endosomal compartments, FcRn inhibitors appeared to traffic through recycling compartments in a similar manner in HUVECs, and their return to the cell surface in FcRn-transfected cells occurred with similar kinetics. These data demonstrate the impact of different structural features of FcRn inhibitors on functional outcomes on cells in vitro.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent articular inflammation, cartilage destruction and aberrant synovial angiogenesis. While current cytokine-centric therapies have revolutionized RA management, their limitations highlight the need for a deeper understanding of the integrated synovial microenvironment. This review explores the critical role of exosomes as central regulatory nodes orchestrating intercellular communication within the RA joint. Under conditions of hypoxia and metabolic stress, exosomes secreted by fibroblast-like synoviocytes (FLS) and immune cells are dynamically loaded with pathogenic cargo, including microRNAs and autoantigens. These vesicles actively modulate macrophage phenotypes, moving beyond the traditional binary framework to reflect a continuum of pro-inflammatory activation, reprogram T-cells to favour pathogenic Th17 expansion while impairing regulatory T-cells (Tregs), and amplify autoreactive B-cell activation for sustained autoantibody production. While exosomes sustain the hypoxia-inflammation-angiogenesis axis and promote invasive pannus formation independently of transient soluble cytokines, we critically delineate which of these mechanisms are validated in RA-specific models against broader immunobiology. We propose that targeting these exosome-mediated signalling cascades offers a promising strategy to overcome therapeutic resistance, signifying their potential as novel therapeutic interventions and high-fidelity diagnostic biomarkers. Further, the significant translational, delivery, and standardization challenges are also addressed.