17 research outputs found
Dendritic Cell and Cancer Therapy
Dendritic cells (DCs) are acknowledged as the most potent professional antigen-presenting cells (APCs), able to induce adaptive immunity and support the innate immune response [...
Enhancing Dendritic Cell Cancer Vaccination: The Synergy of Immune Checkpoint Inhibitors in Combined Therapies
Dendritic cell (DC) cancer vaccines are a promising therapeutic approach, leveraging the immune system to fight tumors. These vaccines utilize DCs’ ability to present tumor-associated antigens to T cells, triggering a robust immune response. DC vaccine development has progressed through three generations. The first generation involved priming DCs with tumor-associated antigens or messenger RNA outside the body, showing limited clinical success. The second generation improved efficacy by using cytokine mixtures and specialized DC subsets to enhance immunogenicity. The third generation used blood-derived DCs to elicit a stronger immune response. Clinical trials indicate that cancer vaccines have lower toxicity than traditional cytotoxic treatments. However, achieving significant clinical responses with DC immunotherapy remains challenging. Combining DC vaccines with immune checkpoint inhibitors (ICIs), such as anticytotoxic T-lymphocyte Antigen 4 and antiprogrammed death-1 antibodies, has shown promise by enhancing T-cell responses and improving clinical outcomes. These combinations can transform non-inflamed tumors into inflamed ones, boosting ICIs’ efficacy. Current research is exploring new checkpoint targets like LAG-3, TIM-3, and TIGIT, considering their potential with DC vaccines. Additionally, engineering T cells with chimeric antigen receptors or T-cell receptors could further augment the antitumor response. This comprehensive strategy aims to enhance cancer immunotherapy, focusing on increased efficacy and improved patient survival rates
Cerebrospinal fluid cytokine expression profile in multiple sclerosis and chronic inflammatory demyelinating polyneuropathy
Background: Cerebrospinal fluid (CSF) analysis in patients with particular neurologic disorders is a powerful tool to evaluate specific central nervous system inflammatory markers for diagnostic needs, because CSF represents the specific immune micro-environment to the central nervous system.
Methods: CSF samples from 49 patients with multiple sclerosis (MS), Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and non-inflammatory neurologic disorders (NIND) as controls were submitted to protein expression profiles of 47 inflammatory biomarkers by multiplex Luminex bead assay to investigate possible differences in the inflammatory process for MS and CIDP.
Results: Our results showed differences in CSF cytokine levels in MS and CIDP, in particular IL12 (p40) was significantly highly expressed in MS in comparison with CIDP and NIND, while SDF-1 and SCGF- were significantly highly expressed in CIDP cohort when compared to MS and NIND. IL-9, IL-13, and IL-17 had higher expression levels in NIND if compared with the other groups.
Conclusions: Our study showed that, despite some common pathogenic mechanisms, central and peripheral nervous system demyelinating diseases, such as MS and CIDP, differ in some specific inflammatory soluble proteins in CSF, underlining differences in the immune response involved in those autoimmune disease
Circulating dendritic cells deficiencies as a new biomarker in classical Hodgkin lymphoma
No robust biomarkers have been yet validated to identify the recurrence of disease in classical Hodgkin Lymphoma (cHL) patients upon induction treatment. The relevance of the inflammatory microenvironment in cHL prompted us to investigate the key immunomodulator myeloid dendritic cells type-1 (mDC1), type-2 (mDC2) and plasmacytoid dendritic cells (pDC). Blood DC levels were assessed in 52 newly diagnosed patients through multiparametric flow-cytometry. All but two patients received ABVD regimen (doxorubicin, bleomycin, vinblastine, dacarbazine). The median counts of all DC subsets were lower in cHL patients than in healthy controls (P < 0·001). Median mDC counts were inferior for the advanced vs early stage patients for both mDC1s and mDC2s (P = 0·008; P = 0·0007 respectively). Also, median mDC2 counts were reduced in case of bulky (P = 0·0004) and extra-nodal (P = 0·046) disease. Patients with B symptoms had lower levels for mDC1s (P = 0·046), mDC2s (P = 0·009) and pDCs (P = 0·040). All the DC subtypes increased at the end of treatment in 26 patients (P < 0·001): 4·6-fold for mDC1, 2·4-fold for mDC2, 4·5-fold for pDC and aligned DCs subsets with the reference frequencies and the interquartile ranges of the controls. In conclusion, DCs may contribute to the disturbed immunological interplay typical of cHL, prompting a further evaluation of their value as a potential new biomarker
Multiplex array analysis of circulating cytokines and chemokines in natalizumab-treated patients with multiple sclerosis
Natalizumab greatly reduces inflammatory relapses in multiple sclerosis (MS) by blocking the integrin-mediated leukocyte traffic to the brain, but less is known about its effects on the systemic immunity. We measured 48 cytokines/chemokines in sera from 19 natalizumab-treated MS patients. Serum concentrations of both anti-(IL-10, IL1ra) and pro-inflammatory (IL7, IL16) molecules decreased after 21-month treatment, without associations to unbalanced Th2/Th1cytokine ratios, clinical responses, and blood/urine replication of polyomavirus JC (JCPyV). No patient developed the JCPyV-related progressive multifocal leukoencephalopathy (PML), the major risk factor of natalizumab therapy. Our data suggest that natalizumab has marginal impact on the systemic immunity
Merkel Cell Polyomavirus Is Associated with Anal Infections in Men Who Have Sex with Men
Background: Viral infections of the anal/rectal tract of men who have sex with men (MSM) have been poorly studied. Methods: In total, 158 swab samples (81 anal/rectal, 65 throat/oral and 12 urethral) were collected from 126 MSM. DNA was isolated and subjected to real-time PCR assays for the detection of the sexually transmitted (ST) pathogens Chlamydia trachomatis, Neisseria gonorrhoeae and Mycoplasmas ssp, human papillomavirus (HPV) and six human polyomaviruses (HPyVs; JCPyV, BKPyV, Merkel cell PyV⁻MCPyV-, HPyV-6, HPyV-7 and HPyV-9). Results: C. trachomatis (31/126, 24.6%) and M. genitalium (30/126, 23.8%) were the most frequently detected ST pathogens. Thirty-one/126 (24.6%) patients were positive for at least one HPyV. The significantly (p < 0.05) prevalent HPyV in the anal tract was MCPyV, which was amplified in 27/81 (33.3%) samples, followed by HPyV-6, which was amplified in 6/81 (7.4%) swabs. Coinfections with MCPyV and C. trachomatis or Mycoplasmas were found in 4/21 (19.0%) and 5/21 (23.8%) anal/rectal swabs, respectively. Three/4 MCPyV-C. trachomatis coinfected patients were symptomatic. Conclusions: Based on the high prevalence of MCPyV in the anal/rectal swabs from MSM patients and on the well-known oncogenic properties of MCPyV, sexual transmission and possible involvement of HPyVs in the pathogenesis of diseases of the anal canal should be further studied
Photobiomodulation modulates inflammation and oral microbiome : a pilot study
Introduction: Oral mucositis (OM) is a severe side effect in patients undergoing anticancer therapies, which negatively impacts on their quality of life often leading to either the interruption of the therapy. Photobiomodulation (PBM) is emerging as an effective strategy allowing a faster wound healing.
Objectives: This pilot study aims at verifying whether PBM modulates the inflammatory response in patients and its effect on the oral microbiome composition.
Materials and methods: Buccal swabs were collected from four patients affected by OM, both on ulcerated and clinically healthy areas, before and on the last day of PBM therapy, as well as on the first day after treatment discontinuation. The concentration of 38 cytokines and the composition of oral microbiome were measured.
Results: Most of the pro-inflammatory cytokines were reduced, whereas anti-inflammatory cytokines resulted up-regulated by PBM. In addition, PBM influenced the composition of oral microbiome, by decreasing the amount of pathogenic species and promoting the growth of commensal bacteria. These changes were even more evident when separately analysing patients who clinically responded to PBM and the only patient who did not respond.
Conclusions: PBM reduces inflammatory burden in patients affected by OM and positively influences the composition of the oral microbiome
Subclinical impairment of dynamic left ventricular systolic and diastolic function in patients with obstructive sleep apnea and preserved left ventricular ejection fraction.
BACKGROUND: Hypoxia affects myocardial oxygen supply resulting in subclinical cardiac dysfunction in obstructive sleep apnea (OSA) patients, with cardiovascular complications being associated with increased oxidative burst (OB). The aims of our study were to assess left ventricular (LV) dynamic myocardial deformation and diastolic reserve at rest and upon exercise, along with OB determination in this patients subset. METHODS: Conventional echocardiography, Doppler myocardial imaging and LV 2D speckle tracking echocardiography were performed in 55 OSA patients with preserved LV ejection fraction (EF) and 35 age and sex-comparable healthy controls. Peripheral OB levels were evaluated by flow cytometry. RESULTS: Despite comparable LVEF, LV global longitudinal strain (GLS) was significantly reduced in OSA at rest (- 13.4 ± 3.8 vs - 18.4 ± 3.3 in controls, P <  0.001) and at peak exercise (- 15.8 ± 2.6 vs - 23.4 ± 4.3, P <  0.001). Systolic pulmonary artery pressure (sPAP) and E/E' ratios increase during effort were higher in OSA than in controls (ΔsPAP 44.3% ± 6.4 vs 32.3% ± 5.5, P <  0.0001, and ΔE/E' 87.5% ± 3.5 vs 25.4% ± 3.3, P <  0.0001, respectively). The best correlate of E/E' at peak stress was peak exertion capacity (r = - 0.50, P <  0.001). OB was also increased in OSA patients (P = 0.001) but, unlike OSA severity, was not associated with LV diastolic dysfunction. CONCLUSIONS: Evaluation of diastolic function and myocardial deformation during exercise is feasible through stress echocardiography. OSA patients with preserved LVEF show subclinical LV systolic dysfunction, impaired LV systolic and diastolic reserve, reduced exercise tolerance, and increased peripheral levels of OB. Therapy aimed at increasing LV diastolic function reserve might improve the quality of life and exercise tolerability in OSA patients
Multiplex array analysis of circulating cytokines and chemokines in COVID-19 patients during the first wave of the SARS-CoV-2 pandemic in Milan, Italy
Abstract Background The systemic inflammatory syndrome called “cytokine storm” has been described in COVID-19 pathogenesis, contributing to disease severity. The analysis of cytokine and chemokine levels in the blood of 21 SARS-CoV-2 positive patients throughout the phases of the pandemic has been studied to understand immune response dysregulation and identify potential disease biomarkers for new treatments. The present work reports the cytokine and chemokine levels in sera from a small cohort of individuals primarily infected with SARS-CoV-2 during the first wave of the COVID-19 pandemic in Milan (Italy). Results Among the 27 cytokines and chemokines investigated, a significant higher expression of Interleukin-9 (IL-9), IP-10 (CXCL10), MCP-1 (CCL2) and RANTES (CCL-5) in infected patients compared to uninfected subjects was observed. When the change in cytokine/chemokine levels was monitored over time, from the hospitalization day to discharge, only IL-6 and IP-10 showed a significant decrease. Consistent with these findings, a significant negative correlation was observed between IP-10 and anti-Spike IgG antibodies in infected individuals. In contrast, IL-17 was positively correlated with the production of IgG against SARS-CoV-2. Conclusions The cytokine storm and the modulation of cytokine levels by SARS-CoV-2 infection are hallmarks of COVID-19. The current global immunity profile largely stems from widespread vaccination campaigns and previous infection exposures. Consequently, the immunological features and dynamic cytokine profiles of non-vaccinated and primarily-infected subjects reported here provide novel insights into the inflammatory immune landscape in the context of SARS-CoV-2 infection, and offer valuable knowledge for addressing future viral infections and the development of novel treatments