Monocyte-derived dendritic cell (DC)-based vaccines loaded with tumor self-antigens represent a novel approach in anticancer therapy. We evaluated DC-based anticancer immunotherapy (ITx) in an academic Phase I/II clinical trial for children, adolescent, and young adults with progressive, recurrent, or primarily metastatic high-risk tumors. The primary endpoint was safety of intradermal administration of manufactured DCs. Here, we focused on relapsing high-risk sarcoma subgroup representing a major diagnosis in DC clinical trial. As a part of peripheral blood immunomonitoring, we evaluated quantitative association between basic cell-based immune parameters. Furthermore, we describe the pattern of these parameters and their time-dependent variations during the DC vaccination in the peripheral blood immunograms. The peripheral blood immunograms revealed distinct patterns in particular patients in the study group. As a functional testing, we evaluated immune response of patient T-cells to the tumor antigens presented by DCs in the autoMLR proliferation assay. This analysis was performed with T-cells obtained prior to DC ITx initiation and with T-cells collected after the fifth dose of DCs, demonstrating that the anticancer DC-based vaccine stimulates a preexisting immune response against self-tumor antigens. Finally, we present clinical and immunological findings in a Ewing's sarcoma patient with an interesting clinical course. Prior to DC therapy, we observed prevailing CD8+ T-cell stimulation and low immunosuppressive monocytic myeloid-derived suppressor cells (M-MDSC) and regulatory T-cells (Tregs). This patient was subsequently treated with 19 doses of DCs and experienced substantial regression of metastatic lesions after second disease relapse and was further rechallenged with DCs. In this patient, functional testing of autologous T-cell activation by manufactured DC medicinal product during the course of DC ITx revealed that personalized anticancer DC-based vaccine stimulates a preexisting immune response against self-tumor antigens and that the T-cell reactivity persisted for the period without DC treatment and was further boosted by DC rechallenge. : EudraCT 2014-003388-39.
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http://dx.doi.org/10.3389/fonc.2019.01169 | DOI Listing |
Pol J Vet Sci
June 2024
College of Biological Engineering, Henan University of Technology, Zhengzhou, China.
Mannose oligosaccharide (MOS) has been shown to promote animal growth, maintain intestinal health, and activate the intestinal immune system. However, the question of whether MOS can stimulate the immune system and alleviate acetylsalicylic acid (ASA)-induced gut damage remains unresolved. The purpose of this study was to investigate the impact of MOS pretreatment on the immunological and anti-inflammatory capabilities of rats with ASA-induced intestinal injury.
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December 2024
Pathology Advanced Translational Research Unit, Department of Pathology & Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Background: Regulatory T-cells (Tregs) play a crucial role in maintaining immune homeostasis, but their dynamics are altered in a subset of people living with Human Immunodeficiency Virus (HIV) known as immunological non-responders (INRs). INRs fail to reconstitute CD4 T-cell counts despite viral suppression. This study aimed to examine Treg dysregulation in INRs, comparing them to immunological responders (IRs) and healthy controls (HCs).
View Article and Find Full Text PDFFront Biosci (Landmark Ed)
December 2024
Department of Pathology, The First Affiliated Hospital of Soochow University, 215123 Suzhou, Jiangsu, China.
Background: Psoriasis is a chronic and incurable skin inflammation driven by an abnormal immune response. Our study aims to investigate the potential of interferon-γ (IFN-γ) primed mesenchymal stem cells (IMSCs) in targeting T cells to attenuate psoriasis-like inflammation, and to elucidate the underlying molecular mechanism involved.
Methods: Mesenchymal stem cells (MSCs) were isolated from the umbilical cord and identified based on their surface markers.
Front Biosci (Landmark Ed)
December 2024
Mackenzie Cancer Research Group, Department of Pathology and Biomedical Science, University of Otago Christchurch, 8011 Christchurch, Aotearoa New Zealand.
Tumor-associated macrophages (TAMs) are innate immune cells that exert far reaching influence over the tumor microenvironment (TME). Depending on cues within the local environment, TAMs may promote tumor angiogenesis, cancer cell invasion and immunosuppression, or, alternatively, inhibit tumor progression via neoantigen presentation, tumoricidal reactive oxygen species generation and pro-inflammatory cytokine secretion. Therefore, TAMs have a pivotal role in determining tumor progression and response to therapy.
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December 2024
Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, 200011 Shanghai, China.
Most cervical cancers are related to the persistent infections of high-risk Human Papillomavirus (HPV) infections. Increasing evidence has witnessed the immunosuppressive effectiveness of HPV in the oncogenesis steps and progression steps. Here we review the immune response in HPV-related cervical malignancies and discuss the crosstalk between HPVs and the host immune response.
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