Search Results (69)

Although immunotherapy has shown great promise in treating various types of cancer, advanced tumors are often refractory due to a highly immunosuppressive tumor microenvironment (TME). We previously engineered a cancer therapeutic vaccine platform, µGCVax, by co-loading tumor antigen peptides, STING and TLR9 agonists into porous silicon microparticles. While effective in models with lower disease burden, its efficacy against advanced colorectal cancer (CRC) was less promising due to the accumulation of myeloid-derived suppressor cells (MDSCs) in TMEs. In this study, we investigated whether µGCVax-based immunotherapy in advanced CRCs could be potentiated via regulating MDSCs to reprogram the TME. In an advanced CT26 murine CRC model, we assessed µGCVax in combination with oxaliplatin, a standard CRC chemotherapeutic with established immunomodulatory effects. We demonstrated that oxaliplatin was preferentially taken up by monocytic MDSCs (M-MDSCs) and effectively reduced their abundance in the bone marrow, blood, spleen, and tumor. Relief of this immunosuppressive TME increased intratumoral infiltration of antigen-specific CD8⁺ T cells. Ultimately, the combination of oxaliplatin with µGCVax induced robust regression of established CRC tumors. These findings highlight that oxaliplatin synergizes with µGCVax by overcoming MDSC-mediated immunosuppression and enhancing antitumor immunity, representing a promising chemo-immunotherapy strategy for advanced CRC. Full article

We prospectively evaluated whether cytotoxic T-lymphocyte (CTL) activation and T-cell receptor (TCR) Vβ clonality predict treatment-free remission (TFR) after tyrosine kinase inhibitor (TKI) cessation in chronic-phase chronic myeloid leukemia (CML). Forty-five patients with sustained deep molecular response (DMR) were enrolled (On-TKI, n = 38; Off-TKI, n = 7) and underwent one-year immuno-monitoring from consent. The primary endpoint was 12-month TFR, defined as retention of MR4. Overall, 32/45 patients (71%) maintained TFR at 12 months. Longer TKI exposure and stable DMR were associated with TFR; notably, patients fulfilling “≥7 years of TKI plus ≥1 year of DMR” and exhibiting CTL activation features—CD8 > CD4, memory > effector, and/or highly activated CTL clones on TCR Vβ repertoire—showed the highest likelihood of durable TFR. By contrast, NK cells, effector Tregs, and G-/M-MDSCs did not discriminate TFR status in this cohort. Although antigen specificity against CML stem cells was not directly tested, the memory-dominant CTL phenotype is consistent with immune control after antigen reduction. These findings suggest that a simple, clinically accessible strategy based on flow cytometric CTL profiling and TCR Vβ clonality may help inform TKI discontinuation decisions in CML. External validation is warranted to confirm transportability and refine clinical thresholds. Full article

Background/Objectives: Interleukin-6 (IL-6), a pleiotropic cytokine involved in immune regulation, is consistently detected in human semen, even in the absence of overt infection. Its contribution to sperm dysfunction, oxidative stress, and inflammation remains incompletely understood. This study evaluated the associations between seminal IL-6 concentrations and markers of semen quality, oxidative stress, nuclear integrity, and genital tract inflammation in infertile men. Methods: A cohort of 204 infertile men was assessed. Seminal IL-6 was quantified by electrochemiluminescence immunoassay. Semen parameters, malondialdehyde (MDA), catalase (CAT) activity, sperm DNA fragmentation index (DFI), sperm chromatin decondensation index (SDI), leukocytospermia, and bacteriospermia were measured. Analyses included correlation testing, IL-6 threshold stratification (<30, 30–60, 60–100, ≥100 pg/mL), and multivariate regression. Results: IL-6 was detectable in all samples (median: 31.52 pg/mL; range: 1.5–5000 pg/mL). Higher IL-6 levels were significantly associated with reduced sperm concentration, progressive motility, and vitality, and with increased DFI, SDI, MDA, leukocyte counts, and bacteriospermia (p < 0.001). In multivariate models, IL-6 independently predicted reduced progressive motility (β = −0.005; p = 0.032) and elevated leukocyte count (β = 0.0018; p < 0.0001). Logistic regression further showed that IL-6 increased the odds of DFI ≥ 30%, SDI ≥ 30%, and bacteriospermia (p < 0.05). Conclusions: Seminal IL-6 emerges as a sensitive biomarker of immuno-oxidative stress and sperm dysfunction in infertile men. Its integration into clinical evaluation may improve the assessment of inflammatory and oxidative contributors to male infertility. Full article

B-cells and plasmablasts have emerged as central organizers of autoimmune pathogenesis, extending far beyond their classical role as antibody-producing cells to orchestrate immune circuits, tissue microenvironments, and therapeutic trajectories. Advances in single-cell technologies, high-dimensional cytometry, and B-cell receptor sequencing have uncovered a dynamic continuum of B-cell differentiation programs that drive clinical heterogeneity across systemic autoimmune diseases. Plasmablasts, in particular, have gained recognition as highly responsive sensors of immune activation: they expand during flares, encode interferon-driven and extrafollicular responses, and correlate with disease severity. Autoantibody profiles, long viewed as static diagnostic signatures, are now understood as durable molecular footprints of distinct B-cell pathways. In this review, we propose an endotype-based framework integrating B-cell circuits with clinical phenotypes, illustrate therapeutic decision-making through mechanistic case vignettes, and outline future strategies combining immunomonitoring, multi-omics, and precision therapeutics. We further address translational challenges and discuss complementary approaches, including T-cell modulation, FcRn inhibition, and antigen-specific tolerization. Full article

Objective: The objectives of this study were to characterize the clinical, hormonal, and extended biomarker profile of infertile men in a Moroccan context, based on a retrospective single-center study, and to assess the relevance of selected markers for initial andrological assessment. Methods: This descriptive, retrospective, single-center study included 1399 men consulting for infertility between January and December 2024 in a specialized center. Collected data encompassed lifestyle habits, medical history, semen parameters (WHO 2021 criteria), sperm DNA fragmentation (TUNEL assay), nuclear decondensation, and hormonal assays (FSH, testosterone, and inhibin B) available in a subset of 156, 56, and 26 patients (for FSH, testosterone, and inhibin B, respectively). Associations with oligozoospermia were explored using univariate logistic regression analysis. Results: The mean age was 39.0 ± 8.0 years; 57% presented with primary infertility, and 82.8% were active smokers. A sperm concentration <16 M/mL was observed in 31.6% of patients. Among the 156 patients analyzed, high FSH levels were observed in 24% of cases. As for inhibin B, among the 26 patients evaluated, a decrease in levels was observed in 38% of cases. Pathological DNA fragmentation was found in 9.6%. In univariate analysis, oligozoospermia was significantly associated with elevated FSH (OR = 7.25; 95% CI: 3.15–16.70), varicocele (OR = 1.81), and smoking (OR = 0.66). Conclusion: This is the first large-scale Moroccan study integrating advanced biomarkers into the assessment of male infertility. The observed associations between elevated FSH, sperm DNA fragmentation, and varicocele support the development of a simplified andrological triage strategy, particularly relevant in resource-limited settings. Full article

Introduction: Atopic dermatitis (AD) is driven by complex pathways that mediate inflammation and pruritus. The pathophysiology of AD’s disease involves multiple pathways. Interleukin-13 (IL-13) is considered a major cytokine in Th2-type inflammation, responsible for changing the epidermal barrier and producing chronic inflammation, whereas interleukin-31 (IL-31) is considered a major inducer of pruritus. The exact correlation of each of these cytokines with disease severity in children with AD appears to vary across studies. This study was therefore designed to evaluate whether IL-13 and IL-31 levels contribute complementarily or independently to the overall clinical severity of AD in the Moroccan pediatric population and to analyze the correlation between serum IL-13 and IL-31 levels and investigate their correlation with disease severity in a pediatric cohort. Methods: A total of 52 children with moderate to severe AD were included. The severity of the disease was measured using the SCORing Atopic Dermatitis (SCORAD) index. Serum levels of IL-13 and IL-31 were measured by Enzyme-Linked Immunosorbent Assay (ELISA). Results: The IL-13 serum level showed a considerable positive correlation with the SCORAD score (r_s = 0.7, p < 0.0001). On the other hand, IL-31 levels revealed no correlation with SCORAD (r_s = 0.07, p = 0.62) but were positively correlated with pruritus intensity (r_s = 0.91, p < 0.001). Conclusion: Our results support the presence of different pathophysiological axes in pediatric AD, where IL-13 functions as a reliable biomarker of inflammatory severity. IL-31 acts as a systemic marker of the pruritic pathway. Full article

Background/Objectives: A decrease in serum AMH is generally associated with low ovarian response in assisted reproductive procedures, whether or not in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI) is performed. Methods: We report a case involving a 31-year-old woman who had never been pregnant and with irregular menstrual cycles. An ultrasound scan performed on the second day of the cycle showed several annular follicles, a high luteinizing hormone (LH)/follicle-stimulating hormone (FSH) ratio suggesting polycystic ovary syndrome (PCOS), and an undetectable serum level of AMH. Results: Despite these observations, she exhibited an unpredictable hyperresponse during controlled ovarian stimulation, followed by a failed pregnancy despite successful in vitro fertilization with ICSI and a good-quality thawed embryo transfer (4AA). Conclusions: This case highlights the challenges of relying solely on AMH as a predictive marker of ovarian response. Although AMH is widely used for assessing ovarian reserve and stimulation outcomes, its limitations become evident in atypical cases. The paradoxical hyperresponse observed here may result from alternative regulatory mechanisms influenced by elevated LH levels, enhanced gonadotropin receptor sensitivity, or local ovarian factors. This report underscores the need for a personalized, multidimensional approach combining hormonal profiles, ultrasound assessments, and clinical history to optimize stimulation protocols and mitigate risks such as ovarian hyperstimulation syndrome (OHSS). Such tailored protocols are essential for managing patients with complex profiles, particularly those with undetectable AMH levels. Further research is needed to explore the mechanisms behind these atypical ovarian responses, including the roles of genetic polymorphisms, inflammatory markers, and environmental factors. This case demonstrates the importance of cautious interpretation of AMH results and emphasizes the value of comprehensive evaluations in assisted reproductive technologies. Full article

Background/Objectives: Ultrasound-guided transvaginal follicular aspiration is a central procedure in in vitro fertilisation (IVF), aiming to collect oocytes necessary for the success of assisted reproduction treatments. Follicular flushing, proposed in the absence of cumulo-oocyte complex (COC) at initial aspiration, remains controversial regarding its real impact on oocyte quality and pregnancy rates. Methods: In this controlled study, conducted in 274 patients, we evaluated the effects of systematic follicular flushing up to 10 washes with a standardised medium (pH 7.3 ± 0.1; 37.2 ± 0.2 °C) on oocyte yield, oocyte morphology, embryo kinetics and clinical outcomes. Results: Flushing resulted in an additional 38% recovery of COCs, mostly between the second and fifth flush, with no significant increase in oocyte dysmorphisms or major embryonic abnormalities. A slight increase in slow cleavages was observed (27% vs. 23%, p = 0.04), as well as a lower oocyte maturation rate when ovulation was triggered by Ovitrelle alone. Clinically, pregnancy rates per transfer were comparable between groups (33.27% without flushing vs. 32.86% with flushing; p = 0.67), as were miscarriage rates (9.11% vs. 8.69%; p = 0.81). Conclusions: These results indicate that follicular flushing, when applied according to a standardised protocol, significantly increases oocyte yield without compromising oocyte morphological quality or embryonic development potential. Although the observed clinical benefits remain modest, this approach could constitute a relevant complementary strategy, particularly in patients with poor ovarian response or in the context of poor initial recovery. However, the controlled but non-randomised nature of this study requires cautious interpretation of the findings. Larger randomised trials, integrating dynamic assessment technologies, such as time-lapse imaging or oocyte transcriptomic analysis, are needed to refine the clinical indications of this technique and explore its underlying biological mechanisms. Full article

Background/Objectives: Infections of the urogenital tract have experienced renewed interest in recent years, due to their frequency and also their impact on sperm parameters and the fertilizing quality of spermatozoa. Chlamydia trachomatis (CT) represents an intracellular microorganism responsible for sexually transmitted infections (STIs) in men and women. A reliable method of diagnosing this infection is therefore necessary because of the rapid onset of infection and the increase in STI-related diseases and their treatment costs. Methods: We analyzed 2371 semen samples from infertile men and detected the presence anti-CT IgG antibodies by Enzyme-Linked Immunosorbent Assay (ELISA), followed by real-time PCR confirmation of CT DNA whose target is the lipopolysaccharide (LPS). We assessed the effect of CT infections on characteristic parameters of sperm quality, including concentration, motility, viability, and morphology. The impact on sperm DNA quality was assessed by DNA fragmentation index (S) and decondensation of chromatin index (SDI) by the TUNEL technique. Results: Analysis of the results showed significant differences in mobility, concentration, and morphology (p < 0.05) between the control group, positive CT infection with normal spermiogram status (CT+/Normal SG) group, and positive CT infection with abnormal spermiogram status (CT+/Abnormal SG) group. A significant increase in the DFI and the SDI was found between the control group and the case groups, respectively (p < 0.01). Conclusions: Our results confirm that CT infection is associated with significant alterations in sperm parameters and sperm DNA quality. Regular CT screening by qPCR should be encouraged in couples suffering from unexplained infertility. Full article

Local recurrence after breast cancer surgery presents a critical challenge, demanding novel local immunotherapies capable of eliminating residual disease while avoiding systemic toxicity. In situ-forming hydrogels, functionalized with bioactive cargoes, represent a promising platform for precise spatiotemporal drug delivery directly into the post-resection tumor microenvironment. This review comprehensively examines the core design principles governing these advanced materials, highlighting their biocompatibility, stimuli-responsive behavior, tunable mechanics for conforming to surgical cavity, and capacity for multifunctional integration. A key mechanism discussed is how this controlled release profile orchestrates a temporal progression from innate immune activation to robust adaptive immunity. Despite significant promise, translational success faces substantial hurdles, including efficacy validation, scalable manufacturing, regulatory pathway definition, and the lack of predictive biomarkers. Future research priorities include optimizing drug/antigen release kinetics, establishing standardized characterization methods for complex biohybrid systems, and designing adaptive clinical trials incorporating detailed immunomonitoring. By integrating functional biomaterials with immuno-oncology, in situ-forming hydrogels offer a paradigm-shifting approach for postoperative cancer treatment. This review provides a strategic roadmap to accelerate their translation from bench to bedside. Full article

This study aimed to describe phospholipase C zeta (PLCζ) deficiency from patients who experienced oocyte fertilization failure following intracytoplasmic sperm injection (ICSI) and to investigate the relationship between sperm DNA fragmentation, chromatin decondensation, and PLCζ. A total of 135 patients participated in this study—65 fertile men and 70 infertile patients— and semen samples were obtained to analyze concentration, motility, and morphology. PLCζ protein levels were assessed by immunofluorescence and quantitative techniques, DNA fragmentation by TUNEL essay, and chromatin decondensation by aniline blue staining. The proportion of spermatozoa presenting PLCζ was significantly lower in infertile patients (18.41 ± 18.84%) compared to fertile controls (67.31 ± 13.79%) (p < 0.001). A significant decrease in PLCζ protein levels was observed in infertile patients compared to fertile controls, which was the same for localization patterns for each region (acrosomal, equatorial, and combination of these regions). Significant correlations were also observed between sperm parameters and PLCζ levels, DNA fragmentation, and chromatin decondensation. Furthermore, a statistically significant correlation was detected between the percentage of spermatozoa presenting PLCζ and DNA integrity (p < 0.001). In summary, DNA fragmentation and chromatin decondensation are associated with alterations in the localization patterns and reduced protein levels of PLCζ, which may contribute to total fertilization failure. Full article

Reproductive infertility is characterized by the inability to achieve pregnancy after a year or more of unprotected sexual intercourse. This review highlights the significant impact of exposure to both types of heavy metals (essential and non-essential) on the reproductive performance of various species, particularly humans. Heavy metals present a high atomic density and weight, including lead, mercury, cadmium, nickel, chromium, and arsenic, and are delivered into the environment through natural and human activities, posing a threat to ecological systems and human reproductive health. These heavy metals have the potential for bioaccumulation and can adversely affect male fertility and sperm quality due to their role in disrupting endocrine functions, altering hormone levels responsible for sperm production, and inducing oxidative stress. The elevated production of reactive oxygen species (ROS) exceeds the capability of antioxidants and can lead to the alteration of sperm quality. Seminal fluid contains antioxidants like vitamin C, vitamin E, zinc, and selenium to counteract the impacts of ROS and also to preserve the sperm function. This review aims also to explore the impact of heavy metals on sperm quality and their relationship with antioxidant imbalance and ROS. The exposure to heavy metals whether through occupational or environmental means increases the production of ROS and therefore leads to an imbalance of antioxidants production. All these factors have no doubt an impact on male reproductive health. Full article

Cervical cancer (CC), often caused by persistent high-risk HPV infection, is a major health issue for Moroccan women. This study is the first in Morocco to examine how the cervico-vaginal microbiome differs across HPV-related clinical stages. Using 16S rRNA sequencing, the researchers analyzed samples from 247 women—100 healthy controls, 43 hr-HPV⁺ pre-cancer cases, and 104 post-treatment CC cases. In healthy women, Lactobacillus dominated (70%), but it significantly declined in the pre-cancer group (45%, p < 0.01) and remained low post-treatment (50%). Meanwhile, Pseudomonadota and Actinobacteriota increased in pre-cancer samples (up to 25–30%, p < 0.01). Although the alpha diversity remained stable, the beta diversity differed significantly across stages (p = 0.001), but not by HPV status. Post-treatment samples showed a sharp decline in Bacillota (logFC −5, p < 10⁻¹⁵) and increases in Campylobacterota and Fusobacteriota (logFC +6 to +21, p < 10⁻¹⁶). Functionally, chemo-heterotrophy and fermentation declined, while nitrogen fixation and phototrophy rose in pre-cancer cases. Host factors like late menarche, high parity, STIs, and contraceptive use correlated with specific microbiota shifts. Full article

Although vaccine development has primarily focused on inducing neutralizing antibodies, increasing evidence supports an important role of CD8⁺ T cell responses in vaccine effectiveness. Routine assays, which are mainly based on antibody titers, may therefore not accurately reflect the full immune response elicited by vaccination. Assessing antigen-specific T cell responses upon vaccination poses several challenges. A common issue in studying T cells specific to a vaccine antigen is their low frequency in circulation, which can limit their ex vivo analysis. Moreover, the use of human cell-based models is crucial for studying and optimizing the induction of T cell responses to design effective vaccines. We developed an innovative in vitro approach of human CD8⁺ T cell priming, based on the rapid mobilization of dendritic cells (DCs) directly from unfractionated peripheral blood mononuclear cells (PBMCs). This simple and original method allows for side-by-side comparisons of multiple test parameters in a standardized system, providing both quantitative and qualitative readouts of primed antigen-specific CD8⁺ T cells. Here, we discuss the genesis of this approach and its versatile applications, including monitoring antigen-specific T cell responses, evaluating an individual’s T cell priming capacity, and conducting preclinical studies on potential adjuvants and vaccine candidates. Full article

The increasing complexity of dendritic cell (DC)-derived exosome (DEX) immunotherapy demands structured monitoring protocols capable of translating molecular activity into actionable clinical outputs. This study proposes a standardized, multistage immunomonitoring framework designed to evaluate immune activation, cytokine polarization, and product integrity in DEX-based therapies. The protocol integrates open access methodologies—flow cytometry, cytometric bead array (CBA), and Western blotting—to assess CD69/CD25 activation, Th1/Th2/Th17 cytokine profiles, and vesicle identity across distinct checkpoints. These outputs are consolidated within the Structured Immunophenotypic Traceability Platform (STIP), which applies logic-based classifications (Type I–III) to support reproducible stratification of immune responses. Functional validation was performed through ex vivo co-culture models, enabling real-time interpretation of immune polarization, cytotoxic potential, and batch consistency. These outputs are supported by previous experimental validations published in Cancers and Biomedicines (2025), where PLPC and DC-derived vesicles demonstrated immunological consistency and a phenotypic stratification capacity. This approach provides a scalable monitoring structure that can support personalized treatment decisions, quality assurance workflows, and integration into regulatory documentation (e.g., CTD Module 5.3) for early-phase, non-pharmacodynamic immunotherapies. This conceptual protocol does not aim to demonstrate therapeutic efficacy but to provide a reproducible documentation framework for real-world immune monitoring and regulatory alignment in vesicle-based immunotherapy. Full article