المؤلفون: Camille Jacques, Flora Marchand, Mathias Chatelais, Virginie Albinet, Claire Coustal, Ilaria Floris

المصدر: Cancers, Vol 16, Iss 7, p 1421 (2024)

مصطلحات موضوعية: micro-immunotherapy, cytokines, papillomavirus, cervical cancer, HeLa, immune response, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Human papillomavirus (HPV) is the second most common infectious agent causing cancer. Persistent infection with high-risk (HR)-HPV can lead to cervical intra-epithelial neoplasia and cervical carcinomas (CC). While host immune response is necessary for viral clearance, chronic immune activation contributes to a low-grade inflammation that can ultimately lead to carcinogenesis. The micro-immunotherapy medicine (MIM) 2LPAPI® could be a valuable tool to manage the clearance of the virus and reduce the risk of developing CC. In this in vitro study, we aimed to investigate its mode of action. We showed that actives from the MIM increased the IL-6, IFN-γ, and IP-10 secretion in human peripheral blood mononuclear cells (PBMCs) exposed to peptides derived from the HPV-16 capsid (HPV16(L1)). This could reflect an increase in the immune activity toward HPV-16. At the same time, some active substances reduced the lympho-proliferation and the expression of T-cell activation markers. Finally, some of the MIM actives displayed antiproliferative effects in CC-derived HeLa cells under serum-starvation conditions. Altogether, this body of data highlighted for the first time the dual effect of MIM in the framework of HR-HPV infections as a potential (i) immune modulator of HPV16(L1)-treated PBMCs and (ii) antiproliferative agent of HPV-positive CC cells.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2072-6694/16/7/1421Test; https://doaj.org/toc/2072-6694Test

الوصول الحر: https://doaj.org/article/a0a5daac4d77443baa0a9b807a2a6ad0Test

المؤلفون: Camille Jacques, Flora Marchand, Mathias Chatelais, Adrien Brulefert, Mathieu Riffault, Ilaria Floris

المصدر: Life, Vol 14, Iss 3, p 375 (2024)

مصطلحات موضوعية: micro-immunotherapy, low doses, ultra-low doses, interleukin-6, immune cells models, immune responses modulation, Science

الوصف: As one of the major cytokines implicated in the orchestration of immune responses, interleukin 6 (IL-6) can either act as a pro- or an anti-inflammatory factor, depending on the micro-environment. In micro-immunotherapy (MI) medicines, IL-6 is employed at low doses (LD) and ultra-low doses (ULD), expressed in centesimal Hahnemannian (CH), and used alone or in combination with other immune regulators to modulate patients’ immune responses. The present study focused on assessing the in vitro immune-modulatory effects of two IL-6-containing MI products: (i) the unitary IL-6 (4 CH) and (ii) the complex MI-medicine (MIM) 2LALERG®, which includes IL-6 (17 CH) in association with other actives in its formulation. Our results showed that IL-6 (4 CH) activated granulocytes under basal conditions, and natural killer cells in the presence of an anti-CD3 signal, as assessed by their CD69 expression. In addition, IL-6 (4 CH) balanced the macrophages’ differentiation toward a M2a profile. On the other hand, the tested 2LALERG® capsule inhibited the histamine degranulation of rats’ peritoneal mast cells and reduced the release of IL-6 itself in inflamed human macrophages. Altogether, these data provide novel pieces of evidence on the double-edged potential of the LD and ULD of IL-6 in immune responses modulation, when employed in MI.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2075-1729/14/3/375Test; https://doaj.org/toc/2075-1729Test

الوصول الحر: https://doaj.org/article/d9d3379401a141c7b5e1a50ceb360d2aTest

المؤلفون: Camille Jacques, Flora Marchand, Mathias Chatelais, Adrien Brulefert, Ilaria Floris

المصدر: Life, Vol 14, Iss 1, p 102 (2024)

مصطلحات موضوعية: micro-immunotherapy, Epstein–Barr virus, cytokines, immunotherapy, interleukin-2, EBV-associated diseases, Science

الوصف: Background: Epstein–Barr virus (EBV) is often kept silent and asymptomatic; however, its reactivation induces a chronic and/or recurrent infection that is associated with numerous diseases, including cancer and inflammation-related disorders. As no specific treatment is currently available, the immune factors-based micro-immunotherapy (MI) medicine 2LEBV® could be considered a valuable therapeutic option to sustain the immune system in EBV reactivation. Methods: The present work aimed to investigate, for the first time, the effect of 2LEBV® in several in vitro models of uninfected immune-related cells. Results: 2LEBV® displayed phagocytosis-enhancing capabilities in granulocytes. In human peripheral blood mononuclear cells (PBMCs), it increased the intra- and extra-cellular expression of interleukin (IL)-2. Moreover, it modulated the secretion of other cytokines, increasing IL-4, IL-6, and tumor necrosis factor-α levels or lowering other cytokines levels such as IL-9. Finally, 2LEBV® reduced the expression of human leukocyte antigen (HLA)-II in endothelial cells and macrophages. Conclusions: Although these data are still preliminary and the chosen models do not consider the underlying EBV-reactivation mechanisms, they still provide a better understanding of the mechanisms of action of 2LEBV®, both at functional and molecular levels. Furthermore, they open perspectives regarding the potential targets of 2LEBV® in its employment as a therapeutic intervention for EBV-associated diseases.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2075-1729/14/1/102Test; https://doaj.org/toc/2075-1729Test

الوصول الحر: https://doaj.org/article/bb97452c74f84e2ba263218314e93abdTest

المؤلفون: Camille Jacques, Irene Marchesi, Francesco Paolo Fiorentino, Mathias Chatelais, Nicoletta Libera Lilli, Kurt Appel, Beatrice Lejeune, Ilaria Floris

المصدر: International Journal of Molecular Sciences, Vol 23, Iss 11, p 6059 (2022)

مصطلحات موضوعية: micro-immunotherapy, MIM-seq, macrophages, immunomodulation, potential anti-tumor agent, colorectal cancer, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: In this study, the immunomodulatory effects of a sequential micro-immunotherapy medicine, referred as MIM-seq, were appraised in human primary M1 and M2 macrophages, in which the secretion of pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-12, IL-23, and tumor necrosis factor (TNF)-alpha, was inhibited. In addition, the potential anti-proliferative effects of MIM-seq on tumor cells was assessed in three models of colorectal cancer (CRC): an in vitro two-dimensions (2D) model of HCT-116 cells, an in vitro tri-dimensional (3D) model of spheroids, and an in vivo model of subcutaneous xenografted mice. In these models, MIM-seq displayed anti-proliferative effects when compared with the vehicle. In vivo, the tumor growth was slightly reduced in MIM-seq-treated animals. Moreover, MIM-seq could slightly reduce the growth of our spheroid models, especially under serum-deprivation. When MIM-seq was combined with two well-known anti-cancerogenic agents, either resveratrol or etoposide, MIM-seq could even further reduce the spheroid’s volume, pointing up the need to further assess whether MIM-seq could be beneficial for CRC patients as an adjuvant therapy. Altogether, these data suggest that MIM-seq could have anti-tumor properties against CRC and an immunomodulatory effect towards the mediators of inflammation, whose systemic dysregulation is considered to be a poor prognosis for patients.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/23/11/6059Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/2f765858aae7451bb8bda22b6919e868Test

المؤلفون: Camille Jacques, Mathias Chatelais, Karim Fekir, Adrien Brulefert, Ilaria Floris

المصدر: International Journal of Molecular Sciences, Vol 23, Iss 4, p 2314 (2022)

مصطلحات موضوعية: micro-immunotherapy, unitary medicine, interferon-γ, homeopathically prepared interferon-γ, centesimal Hahnemannian dilution, immunostimulant, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: As a cytokine, gamma-interferon (IFN-γ) is considered a key player in the fine-tuned orchestration of immune responses. The extreme cellular sensitivity to cytokines is attested by the fact that very few of these bioactive molecules per cell are enough to trigger cellular functions. These findings can, at least partially, explain how/why homeopathically-prepared cytokines, and especially micro-immunotherapy (MI) medicines, are able to drive cellular responses. We focused our fundamental research on a unitary MI preparation of IFN-γ, specifically employed at 4 CH, manufactured and impregnated onto sucrose-lactose pillules as all other MI medicines. We assessed the IFN-γ concentration in the medium after dilution of the IFN-γ (4 CH)-bearing pillules and we evaluated in vitro drug responses in a wide range of immune cells, and in endothelial cells. Our results showed that IFN-γ (4 CH) stimulated the proliferation, the activation and the phagocytic capabilities of primary immune cells, as well as modulated their cytokine-secretion and immunity-related markers’ expression in a trend that is quite comparable with the well-recognized biological effects induced by IFN-γ. Altogether, these data provide novel and additional evidences on MI medicines, and specifically when active substances are prepared at 4 CH, thus suggesting the need for more investigations.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/23/4/2314Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/59845a3b3e694913a749009fdd95213dTest

المؤلفون: Camille Jacques, Mathias Chatelais, Karim Fekir, Louis Fauconnier, Manon Mellier, Dieudonnée Togbe, Ilaria Floris

المصدر: International Journal of Molecular Sciences, Vol 23, Iss 1, p 110 (2021)

مصطلحات موضوعية: low dose, micro-immunotherapy, 2LEID, immunostimulant drug, respiratory infectious diseases, influenza A virus, host defenses, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: This study aimed at evaluating the effects of the micro-immunotherapy medicine (MIM) 2LEID, both in vitro and in vivo, on several components of the innate and adaptive immune system. MIM increased the phagocytic activity of macrophages, and it augmented the expression of the activation markers CD69 and HLA-DR in NK cells and monocytes/macrophages, respectively. The effect of MIM was evaluated in a model of respiratory infection induced by influenza A virus administration to immunocompetent mice in which it was able to improve neutrophil recruitment within the lungs (p = 0.1051) and slightly increased the circulating levels of IgM (p = 0.1655). Furthermore, MIM stimulated the proliferation of CD3-primed T lymphocytes and decreased the secretion of the immunosuppressive cytokine IL-10 in CD14+-derived macrophages. Human umbilical vein endothelial cells were finally used to explore the effect of MIM on endothelial cells, in which it slightly increased the expression of immune-related markers such as HLA-I, CD137L, GITRL, PD-L1 and ICAM-1. In conclusion, the present study suggests that MIM might be a promising nonspecific (without antigen specificity) immunostimulant drug in preventing and early treating respiratory infections, but not only exclusively, as it would gently support several facets of the immune system and host defenses.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/23/1/110Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/44421ab7c95f4fdb8ee663a87d168f19Test

المؤلفون: Bénédicte Brulin, John C. Nolan, Tecla Marangon, Milan Kovacevic, Mathias Chatelais, Pierre Meheust, Jérome Abadie, Louis-Romée Le Nail, Philippe Rosset, Meadhbh Á. Brennan, Pierre Layrolle

المصدر: Cancers, Vol 13, Iss 19, p 4890 (2021)

مصطلحات موضوعية: osteosarcoma, biopsy, organotypic culture, chemotherapy testing, tumour microenvironment, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Improvements in the clinical outcome of osteosarcoma have plateaued in recent decades with poor translation between preclinical testing and clinical efficacy. Organotypic cultures retain key features of patient tumours, such as a myriad of cell types organized within an extracellular matrix, thereby presenting a more realistic and personalised screening of chemotherapeutic agents ex vivo. To test this concept for the first time in osteosarcoma, murine and canine osteosarcoma organotypic models were maintained for up to 21 days and in-depth analysis identified proportions of immune and stromal cells present at levels comparable to that reported in vivo in the literature. Cytotoxicity testing of a range of chemotherapeutic drugs (mafosfamide, cisplatin, methotrexate, etoposide, and doxorubicin) on murine organotypic culture ex vivo found limited response to treatment, with immune and stromal cells demonstrating enhanced survival over the global tumour cell population. Furthermore, significantly decreased sensitivity to a range of chemotherapeutics in 3D organotypic culture relative to 2D monolayer was observed, with subsequent investigation confirming reduced sensitivity in 3D than in 2D, even at equivalent levels of drug uptake. Finally, as proof of concept for the application of this model to personalised drug screening, chemotherapy testing with doxorubicin was performed on biopsies obtained from canine osteosarcoma patients. Together, this study highlights the importance of recapitulating the 3D tumour multicellular microenvironment to better predict drug response and provides evidence for the utility and possibilities of organotypic culture for enhanced preclinical selection and evaluation of chemotherapeutics targeting osteosarcoma.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2072-6694/13/19/4890Test; https://doaj.org/toc/2072-6694Test

الوصول الحر: https://doaj.org/article/6d06623c77f5439480395c42928ad06fTest

المؤلفون: Olivier Espitia, Mathias Chatelais, Marja Steenman, Céline Charrier, Blandine Maurel, Steven Georges, Rémi Houlgatte, Franck Verrecchia, Benjamin Ory, François Lamoureux, Dominique Heymann, Yann Gouëffic, Thibaut Quillard

المصدر: PLoS ONE, Vol 13, Iss 1, p e0191976 (2018)

مصطلحات موضوعية: Medicine, Science

الوصف: Vascular calcification is a strong and independent predictive factor for cardiovascular complications and mortality. Our previous work identified important discrepancies in plaque composition and calcification types between carotid and femoral arteries. The objective of this study is to further characterize and understand the heterogeneity in vascular calcification among vascular beds, and to identify molecular mechanisms underlying this process. We established ECLAGEN biocollection that encompasses human atherosclerotic lesions and healthy arteries from different locations (abdominal, thoracic aorta, carotid, femoral, and infrapopliteal arteries) for histological, cell isolation, and transcriptomic analysis. Our results show that lesion composition differs between these locations. Femoral arteries are the most calcified arteries overall. They develop denser calcifications (sheet-like, nodule), and are highly susceptible to osteoid metaplasia. These discrepancies may derive from intrinsic differences between SMCs originating from these locations, as microarray analysis showed specific transcriptomic profiles between primary SMCs isolated from each arterial bed. These molecular differences translated into functional disparities. SMC from femoral arteries showed the highest propensity to mineralize due to an increase in basal TGFβ signaling. Our results suggest that biological heterogeneity of resident vascular cells between arterial beds, reflected by our transcriptomic analysis, is critical in understanding plaque biology and calcification, and may have strong implications in vascular therapeutic approaches.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC5786328?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/058f2ba2176a48dca805908cb2990c69Test

المؤلفون: Jean-Michel Davaine, Thibaut Quillard, Régis Brion, Olivier Lapérine, Béatrice Guyomarch, Thierry Merlini, Mathias Chatelais, Florian Guilbaud, Meadhbh Áine Brennan, Céline Charrier, Dominique Heymann, Yann Gouëffic, Marie-Françoise Heymann

المصدر: PLoS ONE, Vol 9, Iss 9, p e107642 (2014)

مصطلحات موضوعية: Medicine, Science

الوصف: Background and purposeVascular calcification, recapitulating bone formation, has a profound impact on plaque stability. The aim of the present study was to determine the influence of bone-like vascular calcification (named osteoid metaplasia = OM) and of osteoprotegerin on plaque stability.MethodsTissue from carotid endarterectomies were analysed for the presence of calcification and signs of vulnerability according to AHA grading system. Osteoprotegerin (OPG), pericytes and endothelial cells were sought using immuno-histochemistry. Symptoms and preoperative imaging findings (CT-scan, MRI and Doppler-scan) were analyzed. Human pericytes were cultured to evaluate their ability to secrete OPG and to influence mineralization in the plaque.ResultsSeventy-three carotid plaques (49 asymptomatic and 24 symptomatic) were harvested. A significantly higher presence of OM (18.4% vs 0%, pConclusionsOPG (intraplaque an plasmatic) and OM are associated with carotid plaque stability. Pericytes may be involved in the secretion of intraplaque OPG and in the formation of OM.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/4b4a0f94d79845ea8e36fb623f213069Test

المؤلفون: Christelle Darrieutort-Laffite, Marie-Astrid Boutet, Mathias Chatelais, Régis Brion, Frédéric Blanchard, Dominique Heymann, Benoit Le Goff

المصدر: Mediators of Inflammation, Vol 2014 (2014)

مصطلحات موضوعية: Pathology, RB1-214

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/0962-9351Test; https://doaj.org/toc/1466-1861Test

الوصول الحر: https://doaj.org/article/9e36fab9d15c42f3bc21b2580a2d08aeTest